About this Journal Submit a Manuscript Table of Contents
Journal of Nucleic Acids
Volume 2012 (2012), Article ID 978384, 10 pages
http://dx.doi.org/10.1155/2012/978384
Review Article

Specific Roles of MicroRNAs in Their Interactions with Environmental Factors

Juan Wang1,2,3 and Qinghua Cui1,2,3

1Department of Biomedical Informatics, Peking University Health Science Center, Beijing 100191, China
2MOE Key Lab of Cardiovascular Sciences, Peking University, Beijing 100191, China
3Institute of Systems Biomedicine, Peking University, Beijing 100191, China

Received 4 July 2012; Accepted 26 September 2012

Academic Editor: Kenneth K. W. To

Copyright © 2012 Juan Wang and Qinghua Cui. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

MicroRNAs (miRNAs) have emerged as critical regulators of gene expression by modulating numerous target mRNAs expression at posttranscriptional level. Extensive studies have shown that miRNAs are critical in various important biological processes, including cell growth, proliferation, differentiation, development, and apoptosis. In terms of their importance, miRNA dysfunction has been associated with a broad range of diseases. Increased number of studies have shown that miRNAs can functionally interact with a wide spectrum of environmental factors (EFs) including drugs, industrial materials, virus and bacterial pathogens, cigarette smoking, alcohol, nutrition, sleep, exercise, stress, and radiation. More importantly, the interactions between miRNAs and EFs have been shown to play critical roles in determining abnormal phenotypes and diseases. In this paper, we propose an outline of the current knowledge about specific roles of miRNAs in their interactions with various EFs and analyze the literatures detailing miRNAs-EFs interactions in the context of various of diseases.

1. Introduction

MicroRNAs (miRNAs) are regulatory RNAs that are 20–30 nucleotides long that bind the 3′-untranslated regions of target mRNAs [13]. miRNAs have emerged as critical regulators of gene expression by modulating the expression of numerous target mRNAs mainly at the posttranscriptional level [4]. Since partial or imperfect complementarity of an miRNA to a target mRNA can lead to translational repression, a single miRNA has the ability of regulating a large number of genes [5]. miRNAs have been shown to play a role in regulating a wide range of biological processes, such as cell growth, proliferation, differentiation, development, and apoptosis [6]. In terms of their importance, dysfunction of miRNAs has been associated with various diseases [79]. In contrast to the wealth of publications about their biological effects, the information about specific regulations of miRNAs has comparatively lagged behind.

The phenotype of an organism is determined by the complex interactions between genetic factors (GFs) and environmental factors (EFs). EFs have been shown to contribute tremendously to the formation and development of many diseases, especially complex diseases [1012]. The interactions between GFs and EFs, often hypothesized to be mediated by epigenetic mechanisms, modulate the reproductive fitness of an organism, its response to external stimuli and health [13]. Similar to other GFs, miRNAs have complex interactions with a wide spectrum of EFs [14]. Recently, increased number of studies have shown that miRNAs can functionally interact with a variety of EFs including drugs [15, 16], industrial materials [17, 18], virus and bacterial pathogens [19, 20], alcohol [2123], cigarette smoking [2426], nutrition [27, 28], sleep [29], exercise [30, 31], stress [32, 33], and radiation [34]. The interactions between miRNAs and these EFs play critical roles in determining phenotypes. The illustration of the specific roles of miRNAs and the patterns of miRNA deregulation in the miRNAs-EFs interactions can help to discover the mechanisms of diseases and drug response therefore providing insights into disease diagnosis, prognosis and novel pharmacologic approaches (Figure 1). In this paper, we propose an outline of the current understanding about specific roles of miRNAs when they are interacting with various EFs and analyze the literatures studying the miRNAs-EFs interactions in the context of diseases.

978384.fig.001
Figure 1: Significant roles of miRNAs-EFs interactions.

2. Drugs

Previous studies had highlighted the post-transcriptional modifications mediated by miRNAs in drug treatment, drug sensitivity, and drug addiction.

Several groups have shown the altered miRNAs profiles in anticancer drugs treatment, including all-trans-retinoic acid [35, 36], hydroxycamptothecin [37, 38], imatinib [16, 3941], 5-fluorouracil [42, 43], gemcitabine [4447], cisplatin [4852], fludarabine [53], lithium [5456], epigallocatechin gallate [57], and curcumin [5860]. Garzon et al. studied the effects of all-trans-retinoic acid (ATRA) treatment on the expression of miRNAs in acute promyelocytic leukemia patients as well as in cell lines by using a miRNA microarray platform and quantitative real-time polymerase chain reaction (qRT-PCR). Their results showed upregulation of miR-15a, 15b, 16-1, 223, 342 107 and let-7a-3, let-7c, let-7d and downregulation of miR-181b in ATRA treatment. Among the upregulated miRNAs, miR-107 was predicted to target NFI-A, a gene involved in the regulatory loop with the participation of miR-223 and C/EBPa during granulocytic differentiation [35].

Drug insensitivity or resistance is a major obstacle for successful cancer therapy. Increasing evidence suggested that miRNAs modulate cellular sensitivity to anticancer reagents. Wu et al. showed significantly different sensitivities of the six gastric cancer cell lines to hydroxycamptothecin (HCPT). The levels of 25 miRNAs were shown to be deregulated in the HCPT-resistant gastric cancer cells, including miR-200 family, miR-196a, 338, 126, 31, 98, 7 and let-7 g. The target genes of these miRNAs are involved in cancer development, progression, and chemosensitivity [37]. Ali et al. evaluated the effects of curcumin or its analogue difluorinated-curcumin (CDF) alone or in combination with gemcitabine on cell viability and apoptosis in gemcitabine-sensitive as well as gemcitabine-resistant pancreatic cancer (PC) cell lines [58]. They showed downregulation of miR-200 and upregulation of miR-21 (an indicator of tumor aggressiveness) in gemcitabine-resistant cells in comparison to gemcitabine-sensitive cells. In addition, gemcitabine sensitivity can be induced in PC cells through the modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF. With the application of anti-miR-21 oligonucleotide, Li et al. were able to use anti-miR-21 oligonucleotide to enhance the chemosensitivity of leukemic HL60 cells to arabinosylcytosine [61]. In the study performed by Ji et al. in 2009, the expression patterns of miRNAs in patients with hepatocellular carcinoma (HCC), their survival, and response to interferon alfa were examined [62]. They found a higher expression of miR-26a and miR-26b in non-tumor liver tissue in female than in male HCC patients. They also showed significantly decreased levels of miR-26 expression in comparison to the paired noncancerous tissues. Furthermore, cancer patients with tumors of low miR-26 level had shorter overall survival but better response to interferon therapy than those with tumors of high levels of miR-26. These results suggested the association between the miR-26 expression level and the survival of HCC patients as well as their response to adjuvant interferon alfa therapy [62].

Drug abuse induces persistent structural and functional changes in the mesolimbic dopaminergic system and leads to the progression of patients toward the high-risk drug-seeking behavior and relapse. Much emerging evidence suggests that drug-induced neuroplasticity is regulated by gene expression and post-transcriptional regulation [63, 64]. Chandrasekar and Dreyer had shown that a chronic usage of cocaine decreased miR-124 and let-7d levels and increased the expression of miR-181a in mesolimbic pathway [65]. They also proposed a complex regulatory pathway involving miRNAs in cocaine-mediated neuronal adaptations [66]. Evidence has suggested that cross-regulation between transcription factors and miR-212/132 played a role in drug addiction [67]. MiR-132 and miR-212 are tandem miRNAs whose expression is necessary for the proper development, maturation, and function of neurons. Deregulation of miR-212/132 had been associated with several neurological disorders [67]. It has been shown that overexpression of miR-212 induces CREB activity, the negative modulator of the reward response to cocaine, therefore exerts protective function against cocaine addiction by reducing the responsiveness to the motivational properties of the drug [68]. The X-linked transcriptional repressor methyl CpG binding protein 2 (MeCP2), known for its role in the neurodevelopmental disorder Rett syndrome, is emerging as an important regulator of neuroplasticity in postmitotic neurons. MeCP2 regulates cocaine intake through homeostatic interactions with miR-212 to control the effects of cocaine on striatal brain-derived neurotrophic factor (BDNF) levels. As MeCP2 levels are correlated to BDNF expression, which controls cocaine intake, miR-212 could fine-tune the responses of patients to drug abuse by both increasing CREB signaling and decreasing BDNF expression, leading to decreased cocaine intake [69].

3. Industrial Materials

Many industrial materials have toxicity and may alter developmental pathways and cell processes through epigenetic mechanisms. Bisphenol A (BPA) is an industrial plasticizer widely used as coating for food cans and plastic water bottles. The frequency of BPA exposure has steadily increased during recent years [18]. Whiting and colleagues investigated the effects of BPA exposure on miRNAs in human placental cell lines using miRNA microarray and qRT-PCR analysis. MiR-146a was shown to be the only miRNA validated by qRT-PCR as being significantly upregulated in both 3A and HTR-8 cell lines with BPA treatment [17]. It was also demonstrated that stable overexpression of miR-146a in 3A placental cell line leads to a significant decrease in cell proliferation, a result consistent with several other studies [70, 71]. In addition, over-expression of miR-146a in placental cell lines led to increased sensitivity of these cells to bleomycin, the DNA damaging agent, suggesting that the targets of miR-146a may be involved in the DNA damage response.

Jardim et al. investigated the pollutant-mediated regulations of miRNAs in airway epithelial cells with diesel exhaust particles (DEP), the largest source of emitted airborne particulate matter (PM).They showed that DEP exposure significantly modulated the miRNA expression profile in human airway epithelial cell lines. Specifically, 197 out of 313 (62.9%) detectable miRNAs had been either upregulated or downregulated by 1.5 fold. Molecular network analysis of putative targets of the 12 mostly altered miRNAs suggested that DEP exposure was associated with inflammatory responsive pathways and a strong tumorigenic disease signature. These results clearly demonstrated that alteration of miRNA expression profiles by environmental pollutants such as DEP could modify cellular processes by regulation of gene expression and subsequently lead to disease pathogenesis [72]. In a similar study, Bollati et al. discovered the significant increases of the expression of miR-222 and miR-21 in peripheral blood leukocytes from foundry workers with exposure to metal-rich particulate matter [73].

4. Virus and Other Pathogens

miRNAs have been known to play a critical role in the life cycle of retroviruses and a few oncogenic viruses, including HIV [74, 75], reticuloendotheliosis virus strain T (REV-T) [76], influenza A virus [77], Epstein-Barr virus [78, 79], human T-cell leukemia virus type 1 (HTLV-1) [80, 81], gammaretrovirus XMRV [82], cytomegalovirus (HCMV) [83, 84], Hepatitis B virus (HBV) [85, 86], Hepatitis C virus (HCV) [87, 88], and human papilloma virus (HPV) [89]. These viruses regulate viral replication in the host cells with the mediation of specific miRNAs. HCC is the fifth most common cancer worldwide. The greatest risk factor for HCC is the existence of cirrhosis, most commonly induced by HBV or HCV infections as well as factors such as alcohol consumption, oxidative stress, and aflatoxin or arsenic exposure. Specific miRNAs have been shown to be involved in subgroups of HCC caused by different environmental risk factors. Examinations of miRNAs functions and their expression are important for HCC diagnosis, treatment, and prognosis (Figure 2). Several host cell factors including liver-specific miR-122 have been shown to be involved in virus translation, replication, and production. Jopling et al. observed that sequestration of miR-122 in liver cells could result in marked loss of autonomously replicating hepatitis C viral RNAs. MiR-122 has been shown to increase HCV abundance in HCV replication models by interacting with the 5′ noncoding region (NCR) of the HCV genome [90]. MiR-122 has also been shown to stimulate HCV translation by enhancing the association of ribosome with viral RNA at an early initiation stage [91]. Studies by Lanford and colleagues suggested that miR-122 was essential for the accumulation of HCV RNA in chronically HCV-infected chimpanzees by inhibiting miR-122 through a specific locked nucleic acid (LNA) oligonucleotide [87]. Qiu et al. also suggested a role of miR-122 in the regulation of HBV replication by downregulating the Heme oxygenase-1 (HO-1) [92]. These results suggest that miR-122 may serve as a target for antiviral intervention.

978384.fig.002
Figure 2: Specific miRNAs are associated with different subgroups of HCC associated with various environmental risk factors. ↑ indicates up-regulation; indicates down-regulation; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HBV: hepatitis B virus; AFB1: aflatoxin B1; ROS: reactive oxygen species.

Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent to which the prolonged exposure can cause the adult T-cell leukemia of CD4+ T-cell origin, a severe and fatal lymphoproliferative disease. Pichler et al. reported the deregulation of several miRNAs, including miR-21, 24, 146a, 155, and 223 in HTLV-1-transformed cells. The expression pattern of these miRNAs presented a uniform phenotype in HTLV-transformed cells in comparison to HTLV-negative control cells. Studies suggested miR-146a could be directly attributed to oncoprotein Tax via NF-κB-mediated transactivation in HTLV signaling pathways [81].

Recent studies characterized modifications of host miRNAs expression following infection by exclusively extracellular (Helicobacter pylori) or intracellular (Salmonella enterica) gram-negative bacteria, gram-positive bacteria (Listeria monocytogenes) and other pathogens such as Mycobacterium, Francisella species, and Plasmodium berghei [20, 93, 94].

5. Cigarette Smoking

Throughout one’s life course, a number of exposures can affect an individual’s development, health, and overall quality of life. One of the most common, potentially hazardous environmental exposures that negatively influence health and development is cigarette smoke exposure [24]. Maccani et al. investigated the effects of maternal cigarette smoking during pregnancy on differential expression of miRNAs in the placenta. The data suggested that maternal cigarette smoking during pregnancy was associated with the down-regulation of miR-16, 21, and 146a. They further identified two components, nicotine and benzo [a]pyrene as the specific miRNA modulators in cigarette smoking [26, 95].

Xi et al. investigated the effects of cigarette smoke condensate (CSC) on miRNA expression and function in both normal human respiratory epithelial cells and lung cancer cells [96]. Their results showed that the exposure to CSC induced the expression of miR-31 in both normal respiratory epithelial cells and lung cancer cells. Further studies showed that the overexpression of miR-31 led to increased proliferation and tumorigenicity in lung cancer cells, whereas knockdown of miR-31 expression significantly decreased lung cancer cell proliferation [96]. These results suggested that miR-31 was responsive to cigarette smoke exposure in both normal respiratory epithelia and lung cancer cells and might play a role as an oncomir in lung cancer carcinogenesis pathway [96]. Schembri et al. investigated whole-genome miRNA expression in bronchial airway epithelium from regular smokers and nonsmokers. They observed that 28 miRNAs were differentially expressed, the majority of which were downregulated in the airway epithelium of regular smokers including miR-218 [97]. Several studies have also been performed to characterize the effects of environmental cigarette smoke (ECS) (also called “passive,” “secondhand,” or “sidestream” cigarette smoke) on miRNA expression. Izzotti et al. found that the most greatly downregulated miRNAs belonged to miRNA families which had been previously shown to regulate a number of key biological processes, including stress response, proliferation, angiogenesis, and apoptosis [98]. Furthermore, they showed that exposure to ECS upregulated 2.9% of genes and 9.7% of proteins in the same tissue, suggesting that the ECS exposure-induced down-regulation of miRNAs may lead to increased protein levels of genes which are negatively regulated by these miRNAs [98].

6. Alcohol

Neurotoxicity-mediated pathophysiological conditions could manifest diseases or disabilities such as Parkinson’s and Alzheimer’s which have debilitating implications. Neurotoxicity as well as brain injury can be caused by external agents including drugs andalcohol, and miRNAs have been shown to play a pivotal role in these processes [99]. Maternal ethanol consumption during pregnancy can lead to a stereotypic cluster of fetal craniofacial, cardiovascular, skeletal, and neurological defects that are collectively termed the fetal alcohol spectrum disorder (FASD) [22]. The developing brain is an important and vulnerable target for ethanol. In 2007, Sathyan et al. obtained the first evidence showing that miRNAs mediated the teratogenic effects by ethanol treatment [100]. The accumulated data support the following conclusions. (1) Ethanol appears to affect a relatively small subset of expressed miRNAs. (2) Ethanol appears to affect miRNAs which are normal components of the cellular repertoire for a given stage of differentiation. As an example, miR-124 is sufficient to direct fetal neural stem cells (NSCs) toward a neuronal lineage (22,101). (3) Ethanol appears to affect increasing numbers of miRNAs along the developmental stage. (4) MiRNAs targeted by ethanol exhibit developmental stage-specific sensitivity. (5) Some ethanol-sensitive miRNAs exert their functions over multiple developmental stages, for example, miR-9 exhibits ethanol sensitivity at multiple stages of development, expanding from the embryo through fetus to the adulthood [22, 101, 102]. In order to illustrate the mechanisms of ethanol regulation of miRNAs, Sathyan et al. reported that GABAA receptors and nicotinic acetylcholine receptors could mediate certain ethanol effects on miRNAs expression, respectively [100, 101]. It has been shown that several ethanol-sensitive miRNAs are localized on chromosomal regions that are susceptible to epigenetic modifications. Ligand-gated ion channel receptors and epigenetic modifications have been shown to be potential mediators of the effects of ethanol on fetal miRNAs [22]. Ethanol and nicotine are often coabused. Balaraman et al. studied their combined effects on fetal neural development, particularly on NSCs. Their results showed that ethanol suppressed the expression of known ethanol-sensitive miRNAs (miR-9, 21, 153, and 335) and miR-140-3p, while nicotine at the concentrations attained by cigarette smokers could induce a dose-related induction in these miRNAs. These data suggest that concurrent exposure to ethanol and nicotine disrupts miRNA regulatory networks that are important for NSC maturation [101].

Alcohol-dependence can lead to long-term changes of gene expression in brain. Tapocik et al. examined the potential roles of miRNAs in persistent gene expression regulation of the medial prefrontal cortex (mPFC) of the rats with a history ofalcohol-dependence. Their results showed that more than 41 rat miRNAs and 165 mRNAs in the mPFC were significantly altered after chronicalcoholexposure. Categories of gene ontology differential expression indicated that these miRNAs served in functional processes commonly associated with neurotransmission, neuroadaptation, and synaptic plasticity. Their results demonstrated a significant shift inmiRNAexpression pattern in the mPFC following a history of alcohol-dependence. MiRNAs may play a pivotal role in the reorganization of synaptic connections and long-term neuroadaptations in alcohol-dependence due to their functions of global regulation of multiple target transcripts [23].

Chronicalcoholabuse can cause liver damage, including inflammation, fatty liver, fibrosis, cirrhosis, and HCC. Bala and Szabo showed thatalcoholcould induce miR-155 and miR-132 expression in liver as well as in isolated hepatocytes and Kupffer cells ofalcohol-fed mice [103]. Yin et al. showed that miR-217 could promote ethanol-induced fat accumulation in hepatocytes by downregulating SIRT1 [104]. Ladeiro et al. suggested the miRNA deregulations may be associated with alcohol consumption and HBV infection in HCC. Their studies indicated the correlation between miR-126 down-regulation and alcohol abuse-related HCC in comparison to the other HCCs (Figure 2). Their miRNAs profiling is the first global genomic approach that enables us to differentiate the alcohol abuse-related HCC from the other HCC tumors [21].

7. Stress

Cells frequently encounter conditions that can lead to stress. A few well-characterized stressors include hyperthermia, hypoxia, ATP depletion, and oxidative stress [105, 106]. In order to survive and adapt to stressful conditions, all mammalian cells have evolved a molecular defense reaction termed the cellular stress response (CSR). Recent studies have suggested that miRNAs participate in the CSR, such as hypothermia [107], hyperthermia [108], hypoxia [109112], folate deficiency, and arsenic exposure [33].

Wilmink et al. studied the specific group of deregulated miRNAs in the cells exposed to hyperthermia. Their results showed that the heat could induce upregulation of miRNAs including miR-125b, 382, and 452 and downregulation of miRNAs including miR-138, 7, and 196b. Several thermally-regulated miRNAs (miR-452, 382, and 378) expresses only in cells exposed to hyperthermia [108].

Hypoxia is an essential feature of the neoplastic microenvironment. Tumors with extensive low oxygen level tend to exhibit poor prognosis and resistance to conventional therapy [109]. Ivan’s group identified a set of hypoxia-regulated miRNAs (HRMs), including miR-21, 23a, 23b, 24, 26a, 26b, 27a, 30b, 93, 103, 103, 106a, 107, 125b, 181a, 181b, 181c, 192, 195, 210, and 213 [112]. In addition, a set of miRNAs were down-regulated in hypoxic cells, including miR-15b, 16, 19a, 20a, 20b, 29b, 30b, 30e-5p, 101, 141, 122a, 186, 320, and 197 [113, 114]. Saito et al. suggested the involvement of the miR-130 family in hypoxia-induced expression of hypoxia inducible factor 1α (HIF-1α). MiR-130 family has been identified to target DDX6 mRNA, which is a component of the P-bodies, and facilitate the translation of HIF-1α during hypoxia [110].

Dietary folate deficiency has been linked to developmental anomalies as well as increased risk for a number of cancers [115]. Low dietary folate levels lead to decreased DNA stability through misincorporation of uracil and subsequent DNA damage during the repair process as well as to increased genomic hypomethylation [116]. Arsenic exposure, similar to ionizing radiation and folate deficiency, has been linked to a variety of human cancers [117]. Marsit et al. examined the in vitro effect of folate deficiency and arsenic exposure on the expression pattern of 385 known human miRNAs using microarray analysis and they discovered alterations of specific miRNA profiles. The miRNAs that were significantly altered by 6-day folate deficiency treatment included miR-181b, 182, 222, 345, 181a, 205, 145, 99a, 125b, 130b, 221, 22, 191, 103, 107, 34a, 198, 183, 146, 422b, 210, 24, and 361 [33]. These results suggested that aberrant phenotypes might result from alterations in key miRNAs expression at critical stages in development and tumorigenesis due to altered folate status. Reduced dietary folate could lead to decreased level of S-adenosyl methionine, which is the required methyl-group donor for all cellular methylation reactions, including those for DNA and proteins such as histones [33]. The altered miRNAs expression profiles may be related to the altered methyl-donor pool and the subsequent epigenetic alterations at the DNA or histone code level, resulting in changes of miRNA and gene expression [33]. The miRNAs that were significantly altered by 6-day arsenic exposure included miR-210, 22, 34a, 221, and 222 [33], all of which were also altered by folate deficiency. Similar effects on genomic methylation status have also been reported for arsenic [118]. These results supported the hypothesis that arsenic may alter one-carbon metabolism and therefore cause downstream epigenetic effects.

8. Radiation

DNA damage can be caused by multiple stressors including ionizing radiation, UV exposure, reactive oxygen species, and many DNA damaging chemicals, such as doxorubicin and camptothecin [119121]. MiRNA-mediated gene regulation has been contributed to the mechanisms of DNA-damage caused by UV exposure and ionizing radiation. Studies by Pothof et al. suggested that the cellular responses to UV-induced DNA damage were also regulated at the post-transcriptional level by miRNAs. UV damage has been shown to cause cell-cycle-dependent relocalization of Ago2 into stress granules and changes of miRNA expression. Both events of miRNA-expression alteration and stress-granule formation occurred within the first hour following genotoxic stress, which suggested miRNAs-mediated gene regulation happened earlier than most transcriptional responses. The functionality of the miRNAs response was illustrated by the UV-inducible miR-16 which down-regulated checkpoint-gene CDC25a and regulated cell proliferation [122].

Ionizing radiation (IR) has been widely used in cancer therapy and biological studies. It disrupts cellular homeostasis through multiple mechanisms including the alteration of gene expression profile [123]. Shin et al. investigated the effects of IR on miRNA expression profile in the human lung carcinoma cell line A549. Microarray analysis identified 12 and 18 miRNAs in 20- and 40-Gy-exposed A549 cells, respectively, with more than 2-fold changes in their expression levels. Target prediction for IR-responsive miRNAs suggested that these miRNAs might target genes which are related to apoptosis, regulation of cell cycle, and DNA damage and repair. The results suggested that the expression levels of miRNAs could be affected by radiation and they might be involved in the regulation of radiation responses [123]. Niemoeller et al. investigated IR-induced miRNA expression profiles in six malignant cell lines. Their results showed that IR could cause 2-3 fold change of the expression level of miRNAs known to be involved in the regulation of cellular processes such as apoptosis, proliferation, invasion, local immune response, and radioresistance (e.g., miR-1285, 24-1, 151-5p, and let-7i). Moreover, they discovered several new miRNAs that are radiation-responsive (e.g., miR-144) [34].

Exposure to high-dose radiation causes ionization in the molecules of living cells, leads to DNA damage, and promotes tumor formation. On the other hand, low-dose radiation induces the beneficial effects on organisms, named as hormesis. Cha et al. identified responses of miRNAs to low- or high-dose -irradiation in the human lymphoblast line IM9. They discovered that IR exposure could induce changes in specific miRNA expression in a dose-dependent manner and provided evidence that low-dose radiation could suppress the progression of malignant cancer by controlling miRNA expression [124].

9. Conclusion and Future Directions

Environmental exposures including drugs, industrial materials, cigarette smoking, alcohol, stress, and radiation may cause a number of deleterious effects on health, development, and survival. Increased research has discovered the roles of miRNAs in the responses to environmental exposures under various conditions. The interactions of miRNAs and EFs have been associated with abnormal phenotypes and diseases. For example, specific miRNAs have been identified for different subgroups of HCC with various environmental risk factors. Investigation into the specific roles of miRNAs in the interactions between miRNAs and EFs may help uncovering the mechanisms of disease. These studies may potentially lead to the development of useful indicators of toxic exposure or novel biomarkers for diseases diagnosis. Studies of miRNAs in the disease context may also contribute to the development of novel pharmacologic approaches. The recent development of miRNA derivatives with increased stability and binding efficiency, including anti-microRNA oligonucleotides (AMOs) and LNAs served such purpose [87, 109]. As an example, targeting an HRM which plays a survival role in hypoxia may provide a new angle in targeting a notoriously refractory fraction of tumor cells [109]. Anti-miR-21 oligonucleotide has been shown to enhance the chemosensitivity of leukemic HL60 cells to arabinosylcytosine by inducing apoptosis [61]. Treatment of chronically infected chimpanzees with a LNA-modified oligonucleotide (SPC3649) complementary to miR-122 led to long-lasting suppression of HCV viremia [87]. Furthermore, manipulations of selected miRNAs could synergize with conventional therapies in the treatment of various diseases. Finally, insilico analysis and modeling may help studying patterns among miRNAs, EFs, and diseases and identifying novel strategies for disease diagnosis, treatment, and prognosis [125].

Funding

This work is supported by the National Natural Science Foundation of China (Grant no. 81001481).

Acknowledgment

The authors thank Dr. Zhengying Wang for her contribution to the language corrections.

References

  1. R. C. Lee, R. L. Feinbaum, and V. Ambros, “The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14,” Cell, vol. 75, no. 5, pp. 843–854, 1993. View at Publisher · View at Google Scholar · View at Scopus
  2. R. C. Lee and V. Ambros, “An extensive class of small RNAs in Caenorhabditis elegans,” Science, vol. 294, no. 5543, pp. 862–864, 2001. View at Publisher · View at Google Scholar · View at Scopus
  3. Y. Lee, K. Jeon, J. T. Lee, S. Kim, and V. N. Kim, “MicroRNA maturation: stepwise processing and subcellular localization,” EMBO Journal, vol. 21, no. 17, pp. 4663–4670, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. D. V. Dugas and B. Bartel, “MicroRNA regulation of gene expression in plants,” Current Opinion in Plant Biology, vol. 7, no. 5, pp. 512–520, 2004. View at Publisher · View at Google Scholar · View at Scopus
  5. W. Filipowicz, S. N. Bhattacharyya, and N. Sonenberg, “Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?” Nature Reviews Genetics, vol. 9, no. 2, pp. 102–114, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. D. P. Bartel, “MicroRNAs: genomics, biogenesis, mechanism, and function,” Cell, vol. 116, no. 2, pp. 281–297, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Esquela-Kerscher and F. J. Slack, “Oncomirs—microRNAs with a role in cancer,” Nature Reviews Cancer, vol. 6, no. 4, pp. 259–269, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. C. L. Bartels and G. J. Tsongalis, “Mini-reviews micrornas:novel biomarkers for human cancer,” Clinical Chemistry, vol. 55, no. 4, pp. 623–631, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. M. Lu, Q. Zhang, M. Deng et al., “An analysis of human microRNA and disease associations,” PLoS ONE, vol. 3, no. 10, Article ID e3420, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. A. M. Soto and C. Sonnenschein, “Environmental causes of cancer: endocrine disruptors as carcinogens,” Nature Reviews Endocrinology, vol. 6, no. 7, pp. 363–370, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. U. N. Das, “Obesity: genes, brain, gut, and environment,” Nutrition, vol. 26, no. 5, pp. 459–473, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. W. H. Chow, L. M. Dong, and S. S. Devesa, “Epidemiology and risk factors for kidney cancer,” Nature Reviews Urology, vol. 7, no. 5, pp. 245–257, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. S. M. Reamon-Buettner, V. Mutschler, and J. Borlak, “The next innovation cycle in toxicogenomics: environmental epigenetics,” Mutation Research, vol. 659, no. 1-2, pp. 158–165, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. Q. Yang, C. Qiu, J. Yang, Q. Wu, and Q. Cui, “miREnvironment database: providing a bridge for microRNAs, environmental factors and phenotypes,” Bioinformatics, vol. 27, pp. 3329–3330, 2011.
  15. R. T. Lima, S. Busacca, G. M. Almeida, G. Gaudino, D. A. Fennell, and M. H. Vasconcelos, “MicroRNA regulation of core apoptosis pathways in cancer,” European Journal of Cancer, vol. 47, no. 2, pp. 163–174, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. E. Turrini, S. Haenisch, S. Laechelt, T. Diewock, O. Bruhn, and I. Cascorbi, “MicroRNA profiling in K-562 cells under imatinib treatment: influence of miR-212 and miR-328 on ABCG2 expression,” Pharmacogenet Genomics, vol. 22, pp. 198–205, 2012.
  17. M. Avissar-Whiting, K. R. Veiga, K. M. Uhl et al., “Bisphenol A exposure leads to specific microRNA alterations in placental cells,” Reproductive Toxicology, vol. 29, no. 4, pp. 401–406, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. J. H. Kang, F. Kondo, and Y. Katayama, “Human exposure to bisphenol A,” Toxicology, vol. 226, no. 2-3, pp. 79–89, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. Z. Lin and E. K. Flemington, “MiRNAs in the pathogenesis of oncogenic human viruses,” Cancer Letters, vol. 305, no. 2, pp. 186–199, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Eulalio, L. Schulte, and J. Vogel, “The mammalian microRNA response to bacterial infections,” RNA Biology, vol. 9, no. 6, pp. 742–775, 2012. View at Publisher · View at Google Scholar
  21. Y. Ladeiro, G. Couchy, C. Balabaud et al., “MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations,” Hepatology, vol. 47, no. 6, pp. 1955–1963, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. R. C. Miranda, “MicroRNAs and fetal brain development: implications for ethanol teratology during the second trimester period of neurogenesis,” Frontiers in Genetics, vol. 3, article 77, 2012.
  23. J. D. Tapocik, M. Solomon, M. Flanigan et al., “Coordinated dysregulation of mRNAs and microRNAs in the rat medial 4 prefrontal cortex following a history of alcohol dependence,” The Pharmacogenomics Journal. In press. View at Publisher · View at Google Scholar
  24. M. A. Maccani and V. S. Knopik, “Cigarette smoke exposure-associated alterations to non-coding RNA,” Frontiers in Genetics, vol. 3, article 53, 2012. View at Publisher · View at Google Scholar
  25. A. Izzotti, P. Larghero, C. Cartiglia et al., “Modulation of microRNA expression by budesonide, phenethyl isothiocyanate and cigarette smoke in mouse liver and lung,” Carcinogenesis, vol. 31, no. 5, pp. 894–901, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. M. A. Maccani, M. Avissar-Whiting, C. E. Banister, B. McGonnigal, J. F. Padbury, and C. J. Marsit, “Maternal cigarette smoking during pregnancy is associated with downregulation of miR-16, miR-21 and miR-146a in the placenta,” Epigenetics, vol. 5, no. 7, pp. 583–589, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Alisi, L. Da Sacco, G. Bruscalupi et al., “Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease,” Laboratory Investigation, vol. 91, no. 2, pp. 283–293, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. L. A. Davidson, N. Wang, M. S. Shah, J. R. Lupton, I. Ivanov, and R. S. Chapkin, “n-3 Polyunsaturated fatty acids modulate carcinogen-directed non-coding microRNA signatures in rat colon,” Carcinogenesis, vol. 30, no. 12, pp. 2077–2084, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. C. J. Davis, S. G. Bohnet, J. M. Meyerson, and J. M. Krueger, “Sleep loss changes microRNA levels in the brain: a possible mechanism for state-dependent translational regulation,” Neuroscience Letters, vol. 422, no. 1, pp. 68–73, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Nielsen, C. Scheele, C. Yfanti et al., “Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle,” Journal of Physiology, vol. 588, no. 20, pp. 4029–4037, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. M. J. Drummond, J. J. McCarthy, C. S. Fry, K. A. Esser, and B. B. Rasmussen, “Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids,” American Journal of Physiology, vol. 295, no. 6, pp. E1333–E1340, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. Y. Gidron, M. De Zwaan, K. Quint, and M. Ocker, “Influence of stress and health-behaviour on miRNA expression,” Molecular Medicine Reports, vol. 3, no. 3, pp. 455–457, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. C. J. Marsit, K. Eddy, and K. T. Kelsey, “MicroRNA responses to cellular stress,” Cancer Research, vol. 66, no. 22, pp. 10843–10848, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. O. M. Niemoeller, M. Niyazi, S. Corradini et al., “MicroRNA expression profiles in human cancer cells after ionizing radiation,” Radiation Oncology, vol. 6, no. 1, article 29, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Garzon, F. Pichiorri, T. Palumbo et al., “MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia,” Oncogene, vol. 26, no. 28, pp. 4148–4157, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. S. Das, N. Foley, K. Bryan et al., “MicroRNA mediates DNA demethylation events triggered by retinoic acid during neuroblastoma cell differentiation,” Cancer Research, vol. 70, no. 20, pp. 7874–7881, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. X. M. Wu, X. Q. Shao, X. X. Meng et al., “Genome-wide analysis of microRNA and mRNA expression signatures in hydroxycamptothecin-resistant gastric cancer cells,” Acta Pharmacologica Sinica, vol. 32, no. 2, pp. 259–269, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. J. L. Tong, C. P. Zhang, F. Nie et al., “MicroRNA 506 regulates expression of PPAR alpha in hydroxycamptothecin-resistant human colon cancer cells,” FEBS Letters, vol. 585, pp. 3560–3568, 2011.
  39. E. San José-Enériz, J. Román-Gómez, A. Jiménez-Velasco et al., “MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations,” Molecular Cancer, vol. 8, article 69, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. E. I. Zimmerman, C. M. Dollins, M. Crawford et al., “Lyn kinase-dependent regulation of miR181 and myeloid cell leukemia-1 expression: implications for drug resistance in myelogenous leukemia,” Molecular Pharmacology, vol. 78, no. 5, pp. 811–817, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. Y. Yu, L. Yang, M. Zhao et al., “Targeting microRNA-30a-mediated autophagy enhances imatinib activity against human chronic myeloid leukemia cells,” Leukemia, vol. 26, no. 8, pp. 1752–1760, 2012.
  42. M. Y. Shah, X. Pan, L. N. Fix, M. A. Farwell, and B. Zhang, “5-fluorouracil drug alters the microrna expression profiles in MCF-7 breast cancer cells,” Journal of Cellular Physiology, vol. 226, no. 7, pp. 1868–1878, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. L. Rossi, E. Bonmassar, and I. Faraoni, “Modification of miR gene expression pattern in human colon cancer cells following exposure to 5-fluorouracil in vitro,” Pharmacological Research, vol. 56, no. 3, pp. 248–253, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. T. Boren, Y. Xiong, A. Hakam et al., “MicroRNAs and their target messenger RNAs associated with ovarian cancer response to chemotherapy,” Gynecologic Oncology, vol. 113, no. 2, pp. 249–255, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. J. Hodzic, E. Giovannetti, B. D. Calvo, A. D. Adema, and G. J. Peters, “Regulation of deoxycytidine kinase expression and sensitivity to gemcitabine by micro-RNA 330 and promoter methylation in cancer cells,” Nucleosides, Nucleotides and Nucleic Acids, vol. 30, pp. 1214–1222, 2011.
  46. Q. S. Xia, Y. Ishigaki, L. Sun, R. Chen, and Y. Motoo, “Effect of anti-cancer drugs on the expression of BIC/miR-155 in human pancreatic cancer PANC-1 cells,” Zhonghua Yi Xue Za Zhi, vol. 90, no. 2, pp. 123–127, 2010. View at Scopus
  47. S. Samakoglu, D. S. Deevi, H. Li et al., “Preclinical rationale for combining an EGFR antibody with cisplatin/gemcitabine for the treatment of NSCLC,” Cancer Genomics Proteomics, vol. 9, pp. 77–92, 2012.
  48. A. Sorrentino, C. G. Liu, A. Addario, C. Peschle, G. Scambia, and C. Ferlini, “Role of microRNAs in drug-resistant ovarian cancer cells,” Gynecologic Oncology, vol. 111, no. 3, pp. 478–486, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. W. Zhu, X. Shan, T. Wang, Y. Shu, and P. Liu, “MiR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines,” International Journal of Cancer, vol. 127, no. 11, pp. 2520–2529, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. L. Guo, Y. Liu, Y. Bai, Y. Sun, F. Xiao, and Y. Guo, “Gene expression profiling of drug-resistant small cell lung cancer cells by combining microRNA and cDNA expression analysis,” European Journal of Cancer, vol. 46, no. 9, pp. 1692–1702, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Hummel, D. I. Watson, C. Smith et al., “Mir-148a improves response to chemotherapy in sensitive and resistant oesophageal adenocarcinoma and squamous cell carcinoma cells,” Journal of Gastrointestinal Surgery, vol. 15, no. 3, pp. 429–438, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. Y. Huang, A. Chuang, H. Hao et al., “Phospho-ΔNp63α is a key regulator of the cisplatin-induced microRNAome in cancer cells,” Cell Death and Differentiation, vol. 18, no. 7, pp. 1220–1230, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. E. Moussay, V. Palissot, L. Vallar et al., “Determination of genes and microRNAs involved in the resistance to fludarabine in vivo in chronic lymphocytic leukemia,” Molecular Cancer, vol. 9, article 115, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. R. Zhou, P. Yuan, Y. Wang et al., “Evidence for selective microRNAs and their effectors as common long-term targets for the actions of mood stabilizers,” Neuropsychopharmacology, vol. 34, no. 6, pp. 1395–1405, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. H. Chen, N. Wang, M. Burmeister, and M. G. McInnis, “MicroRNA expression changes in lymphoblastoid cell lines in response to lithium treatment,” International Journal of Neuropsychopharmacology, vol. 12, no. 7, pp. 975–981, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. H. Rong, T. B. Liu, K. J. Yang et al., “MicroRNA-134 plasma levels before and after treatment for bipolar mania,” Journal of Psychiatric Research, vol. 45, no. 1, pp. 92–95, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. W. P. Tsang and T. T. Kwok, “Epigallocatechin gallate up-regulation of miR-16 and induction of apoptosis in human cancer cells,” Journal of Nutritional Biochemistry, vol. 21, no. 2, pp. 140–146, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Ali, A. Ahmad, S. Banerjee et al., “Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF,” Cancer Research, vol. 70, no. 9, pp. 3606–3617, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. C. D. Davis and S. A. Ross, “Evidence for dietary regulation of microRNA expression in cancer cells,” Nutrition Reviews, vol. 66, no. 8, pp. 477–482, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Yang, Y. Cao, J. Sun, and Y. Zhang, “Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells,” Medical Oncology, vol. 27, no. 4, pp. 1114–1118, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. Y. Li, X. Zhu, J. Gu et al., “Anti-miR-21 oligonucleotide enhances chemosensitivity of leukemic HL60 cells to arabinosylcytosine by inducing apoptosis,” Hematology, vol. 15, no. 4, pp. 215–221, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Ji, J. Shi, A. Budhu et al., “MicroRNA expression, survival, and response to interferon in liver cancer,” New England Journal of Medicine, vol. 361, no. 15, pp. 1437–1447, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. C. A. McClung and E. J. Nestler, “Neuroplasticity mediated by altered gene expression,” Neuropsychopharmacology, vol. 33, no. 1, pp. 3–17, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Z. Pietrzykowski, R. M. Friesen, G. E. Martin et al., “Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol,” Neuron, vol. 59, no. 2, pp. 274–287, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. V. Chandrasekar and J. L. Dreyer, “microRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity,” Molecular and Cellular Neuroscience, vol. 42, no. 4, pp. 350–362, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. V. Chandrasekar and J. L. Dreyer, “Regulation of MiR-124, Let-7d, and MiR-181a in the accumbens affects the expression, extinction, and reinstatement of cocaine-induced conditioned place preference,” Neuropsychopharmacology, vol. 36, no. 6, pp. 1149–1164, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. A. Wanet, A. Tacheny, T. Arnould, and P. Renard, “miR-212/132 expression and functions: within and beyond the neuronal compartment,” Nucleic Acids Research, vol. 40, pp. 4742–4753, 2012.
  68. J. A. Hollander, H. I. Im, A. L. Amelio et al., “Striatal microRNA controls cocaine intake through CREB signalling,” Nature, vol. 466, no. 7303, pp. 197–202, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. H. I. Im, J. A. Hollander, P. Bali, and P. J. Kenny, “MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212,” Nature Neuroscience, vol. 13, no. 9, pp. 1120–1127, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. S. L. Lin, H. Kim, and S. Y. Ying, “Intron-mediated RNA interference and microRNA (miRNA),” Frontiers in Bioscience, vol. 13, no. 6, pp. 2216–2230, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. D. Bhaumik, G. K. Scott, S. Schokrpur, C. K. Patil, J. Campisi, and C. C. Benz, “Expression of microRNA-146 suppresses NF-κB activity with reduction of metastatic potential in breast cancer cells,” Oncogene, vol. 27, no. 42, pp. 5643–5647, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. M. J. Jardim, R. C. Fry, I. Jaspers, L. Dailey, and D. Diaz-Sanchez, “Disruption of MicroRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways,” Environmental Health Perspectives, vol. 117, no. 11, pp. 1745–1751, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. V. Bollati, B. Marinelli, P. Apostoli et al., “Exposure to metal-rich particulate matter modifies the expression of candidate MicroRNAs in peripheral blood leukocytes,” Environmental Health Perspectives, vol. 118, no. 6, pp. 763–768, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. X. Wang, L. Ye, Y. Zhou, M. Q. Liu, D. J. Zhou, and W. Z. Ho, “Inhibition of anti-HIV microRNA expression: a mechanism for opioid-mediated enhancement of HIV infection of monocytes,” American Journal of Pathology, vol. 178, no. 1, pp. 41–47, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. G. Sun, H. Li, X. Wu et al., et al., “Interplay between HIV-1 infection and host microRNAs,” Nucleic Acids Research, vol. 40, pp. 2181–2196, 2012.
  76. M. T. Bolisetty, G. Dy, W. Tam, and K. L. Beemon, “Reticuloendotheliosis virus strain T induces miR-155, which targets JARID2 and promotes cell survival,” Journal of Virology, vol. 83, no. 23, pp. 12009–12017, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. Y. J. Ma, J. Yang, X. L. Fan et al., et al., “Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells,” Journal of Cellular and Molecular Medicine, vol. 16, no. 10, pp. 2539–2546, 2012.
  78. N. Motsch, T. Pfuhl, J. Mrazek, S. Barth, and F. A. Grässer, “Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induces the expression of the cellular microRNA miR-146a,” RNA Biology, vol. 4, no. 3, pp. 131–137, 2007. View at Scopus
  79. J. H. Kim, W. S. Kim, and C. Park, “Epstein-Barr virus latent membrane protein-1 protects B-cell lymphoma from rituximab-induced apoptosis through miR-155-mediated Akt activation and up-regulation of Mcl-1,” Leukemia & Lymphoma, vol. 53, no. 8, pp. 1586–1591, 2012.
  80. M. Tomita, Y. Tanaka, and N. Mori, “MicroRNA miR-146a is induced by HTLV-1 tax and increases the growth of HTLV-1-infected T-cells,” International Journal of Cancer, vol. 130, pp. 2300–2309, 2012.
  81. K. Pichler, G. Schneider, and R. Grassmann, “MicroRNA miR-146a and further oncogenesis-related cellular microRNAs are dysregulated in HTLV-1-transformed T lymphocytes,” Retrovirology, vol. 5, article 100, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. K. V. Mohan, K. Devadas, S. Sainath Rao, I. Hewlett, and C. Atreya, “Identification of XMRV infection-associated microRNAs in four cell types in culture,” PLoS ONE, vol. 7, Article ID e32853, 2012.
  83. A. Dittmer and K. Forstemann, “Murine cytomegalovirus infection of cultured mouse cells induces expression of miR-7a,” Journal of General Virology, vol. 93, pp. 1537–1547, 2012.
  84. D. Santhakumar, T. Forster, N. N. Laqtom et al., “Combined agonist-antagonist genome-wide functional screening identifies broadly active antiviral microRNAs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 31, pp. 13830–13835, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. Y. Zhang, Y. Jia, R. Zheng et al., “Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases,” Clinical Chemistry, vol. 56, no. 12, pp. 1830–1838, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. G. L. Zhang, Y. X. Li, S. Q. Zheng, M. Liu, X. Li, and H. Tang, “Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210,” Antiviral Research, vol. 88, no. 2, pp. 169–175, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. R. E. Lanford, E. S. Hildebrandt-Eriksen, A. Petri et al., “Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection,” Science, vol. 327, no. 5962, pp. 198–201, 2010. View at Publisher · View at Google Scholar · View at Scopus
  88. C. Braconi, N. Valeri, P. Gasparini et al., “Hepatitis C virus proteins modulate microRNA expression and chemosensitivity in malignant hepatocytes,” Clinical Cancer Research, vol. 16, no. 3, pp. 957–966, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. M. P. Myklebust, O. Bruland, O. Fluge, A. Skarstein, L. Balteskard, and O. Dahl, “MicroRNA-15b is induced with E2F-controlled genes in HPV-related cancer,” British Journal of Cancer, vol. 105, pp. 1719–1725, 2011.
  90. C. L. Jopling, M. Yi, A. M. Lancaster, S. M. Lemon, and P. Sarnow, “Molecular biology: modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA,” Science, vol. 309, no. 5740, pp. 1577–1581, 2005. View at Publisher · View at Google Scholar · View at Scopus
  91. J. I. Henke, D. Goergen, J. Zheng et al., “microRNA-122 stimulates translation of hepatitis C virus RNA,” EMBO Journal, vol. 27, no. 24, pp. 3300–3310, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. L. Qiu, H. Fan, W. Jin et al., “MiR-122-induced down-regulation of HO-1 negatively affects miR-122-mediated suppression of HBV,” Biochemical and Biophysical Research Communications, vol. 398, no. 4, pp. 771–777, 2010. View at Publisher · View at Google Scholar · View at Scopus
  93. F. El-Assaad, C. Hempel, V. Combes et al., “Differential microRNA expression in experimental cerebral and noncerebral malaria,” Infection and Immunity, vol. 79, no. 6, pp. 2379–2384, 2011. View at Publisher · View at Google Scholar · View at Scopus
  94. D. Delić, M. Dkhil, S. Al-Quraishy, and F. Wunderlich, “Hepatic miRNA expression reprogrammed by Plasmodium chabaudi malaria,” Parasitology Research, vol. 108, no. 5, pp. 1111–1121, 2011. View at Publisher · View at Google Scholar · View at Scopus
  95. M. A. Maccani and C. J. Marsit, “Exposure and fetal growth-associated miRNA alterations in the human placenta,” Clinical Epigenetics, vol. 2, pp. 401–404, 2011.
  96. S. Xi, M. Yang, Y. Tao et al., “Cigarette smoke induces C/EBP-β-mediated activation of mir-31 in normal human respiratory epithelia and lung cancer cells,” PLoS ONE, vol. 5, no. 10, Article ID e13764, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. F. Schembri, S. Sridhar, C. Perdomo et al., “MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 7, pp. 2319–2324, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. A. Izzotti, G. A. Calin, P. Arrigo, V. E. Steele, C. M. Croce, and S. De Flora, “Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke,” The FASEB Journal, vol. 23, no. 3, pp. 806–812, 2009. View at Publisher · View at Google Scholar · View at Scopus
  99. P. Kaur, A. Armugam, and K. Jeyaseelan, “MicroRNAs in neurotoxicity,” Journal of Toxicology, vol. 2012, Article ID 870150, 15 pages, 2012.
  100. P. Sathyan, H. B. Golden, and R. C. Miranda, “Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium,” Journal of Neuroscience, vol. 27, no. 32, pp. 8546–8557, 2007. View at Publisher · View at Google Scholar · View at Scopus
  101. S. Balaraman, U. H. Winzer-Serhan, and R. C. Miranda, “Opposing actions of ethanol and nicotine on microRNAs are mediated by nicotinic acetylcholine receptors in fetal cerebral cortical-derived neural progenitor cells,” Alcoholism: Clinical and Experimental Research, vol. 36, no. 10, pp. 1669–1677, 2012.
  102. T. L. Tal, J. A. Franzosa, S. C. Tilton et al., “MicroRNAs control neurobehavioral development and function in zebrafish,” The FASEB Journal, vol. 26, pp. 1452–1461, 2012.
  103. S. Bala and G. Szabo, “MicroRNA signature in alcoholic liver disease,” International Journal of Hepatology, vol. 2012, Article ID 498232, 6 pages, 2012. View at Publisher · View at Google Scholar
  104. H. Yin, M. Hu, R. Zhang, Z. Shen, L. Flatow, and M. You, “MicroRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down-regulating SIRT1,” The Journal of Biological Chemistry, vol. 287, pp. 9817–9826, 2012.
  105. K. R. Diller, “Stress protein expression kinetics,” Annual Review of Biomedical Engineering, vol. 8, pp. 403–424, 2006. View at Publisher · View at Google Scholar · View at Scopus
  106. B. A. Miller, “The role of TRP channels in oxidative stress-induced cell death,” Journal of Membrane Biology, vol. 209, no. 1, pp. 31–41, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. J. Dresios, A. Aschrafi, G. C. Owens, P. W. Vanderklish, G. M. Edelman, and V. P. Mauro, “Cold stress-induced protein Rbm3 binds 60S ribosomal subunits, alter microRNA levels, and enhances global protein synthesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 6, pp. 1865–1870, 2005. View at Publisher · View at Google Scholar · View at Scopus
  108. G. J. Wilmink, C. L. Roth, B. L. Ibey et al., “Identification of microRNAs associated with hyperthermia-induced cellular stress response,” Cell Stress and Chaperones, vol. 15, no. 6, pp. 1027–1038, 2010. View at Publisher · View at Google Scholar · View at Scopus
  109. R. Kulshreshtha, R. V. Davuluri, G. A. Calin, and M. Ivan, “A microRNA component of the hypoxic response,” Cell Death and Differentiation, vol. 15, no. 4, pp. 667–671, 2008. View at Publisher · View at Google Scholar · View at Scopus
  110. K. Saito, E. Kondo, and M. Matsushita, “MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6,” Nucleic Acids Research, vol. 39, pp. 6086–6099, 2011.
  111. Y. C. Chan, S. Khanna, S. Roy, and C. K. Sen, “MiR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells,” Journal of Biological Chemistry, vol. 286, no. 3, pp. 2047–2056, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. R. Kulshreshtha, M. Ferracin, S. E. Wojcik et al., “A microRNA signature of hypoxia,” Molecular and Cellular Biology, vol. 27, no. 5, pp. 1859–1867, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. Z. Hua, Q. Lv, W. Ye et al., “Mirna-directed regulation of VEGF and other angiogenic under hypoxia,” PLoS ONE, vol. 1, no. 1, article e116, 2006. View at Publisher · View at Google Scholar · View at Scopus
  114. R. B. Donker, J. F. Mouillet, D. M. Nelson, and Y. Sadovsky, “The expression of Argonaute2 and related microRNA biogenesis proteins in normal and hypoxic trophoblasts,” Molecular Human Reproduction, vol. 13, no. 4, pp. 273–279, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. R. Jiang, F. B. Hu, E. L. Giovannucci et al., “Joint association of alcohol and folate intake with risk of major chronic disease in women,” American Journal of Epidemiology, vol. 158, no. 8, pp. 760–771, 2003. View at Publisher · View at Google Scholar · View at Scopus
  116. S. J. James, I. P. Pogribny, M. Pogribna, B. J. Miller, S. Jernigan, and S. Melnyk, “Mechanisms of DNA damage, DNA hypomethylation, and tumor progression in the folate/methyl-deficient rat model of hepatocarcinogenesis,” Journal of Nutrition, vol. 133, pp. 3740S–3747S, 2003. View at Scopus
  117. H. R. Guo, “Cancer risks associated with arsenic in drinking water,” Environmental Health Perspectives, vol. 115, no. 7, pp. A339–A340, 2007. View at Publisher · View at Google Scholar · View at Scopus
  118. H. Chen, S. F. Li, J. Liu, B. A. Diwan, J. C. Barrett, and M. P. Waalkes, “Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation: implications for arsenic hepatocarcinogenesis,” Carcinogenesis, vol. 25, no. 9, pp. 1779–1786, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. S. Bhana and D. R. Lloyd, “The role of p53 in DNA damage-mediated cytotoxicity overrides its ability to regulate nucleotide excision repair in human fibroblasts,” Mutagenesis, vol. 23, no. 1, pp. 43–50, 2008. View at Publisher · View at Google Scholar · View at Scopus
  120. P. Pitsikas, D. Lee, and A. J. Rainbow, “Reduced host cell reactivation of oxidative DNA damage in human cells deficient in the mismatch repair gene hMSH2,” Mutagenesis, vol. 22, no. 3, pp. 235–243, 2007. View at Publisher · View at Google Scholar · View at Scopus
  121. L. Barbour, L. G. Ball, K. Zhang, and W. Xiao, “DNA damage checkpoints are involved in postreplication repair,” Genetics, vol. 174, no. 4, pp. 1789–1800, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. J. Pothof, N. S. Verkaik, W. Van Ijcken et al., “MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response,” EMBO Journal, vol. 28, no. 14, pp. 2090–2099, 2009. View at Publisher · View at Google Scholar · View at Scopus
  123. S. Shin, H. J. Cha, E. M. Lee et al., “Alteration of miRNA profiles by ionizing radiation in A549 human non-small cell lung cancer cells,” International Journal of Oncology, vol. 35, no. 1, pp. 81–86, 2009. View at Publisher · View at Google Scholar · View at Scopus
  124. H. J. Cha, K. M. Seong, S. Bae et al., “Identification of specific microRNAs responding to low and high dose γ-irradiation in the human lymphoblast line IM9,” Oncology Reports, vol. 22, no. 4, pp. 863–868, 2009. View at Publisher · View at Google Scholar · View at Scopus
  125. C. Qiu, G. Chen, and Q. Cui, “Towards the understanding of microRNA and environmental factor interactions and their relationships to human diseases,” Scientific Reports, vol. 2, article 318, 2012. View at Publisher · View at Google Scholar