Lung cancer is the leading cause of cancer death globally. Numerous factors intervene in the onset and progression of lung tumors, among which the participation of lineage-specific transcription factors stands out. Several transcription factors important in embryonic development are abnormally expressed in adult tissues and thus participate in the activation of signaling pathways related to the acquisition of the tumor phenotype. RUNX2 is the transcription factor responsible for osteogenic differentiation in mammals. Current studies have confirmed that RUNX2 is closely related to the proliferation, invasion, and bone metastasis of multiple cancer types, such as osteosarcoma, breast cancer (BC), prostate cancer, gastric cancer, colorectal cancer, and lung cancer. Thus, the present study is aimed at evaluating the role of the RUNX2 transcription factor in inhibiting the apoptosis process. Loss-of-function assays using sh-RNA from lentiviral particles and coupled with Annexin/propidium iodide (PI) assays (flow cytometry), immunofluorescence, and quantitative PCR analysis of genes related to cell apoptosis (BAD, BAX, BCL2, BCL-XL, and MCL1) were performed. Silencing assays and Annexin/PI assays demonstrated that when RUNX2 was absent, the percentage of dead cells increased, and the expression levels of the BCL2, BCL-XL, and MCL1 genes were downregulated. Furthermore, to confirm whether the regulatory role of RUNX2 in the expression of these genes is related to its binding to the promoter region, we performed chromatin immunoprecipitation (ChIP) assays. Here, we report that overexpression of the RUNX2 gene in lung cancer may be related to the inhibition of the intrinsic apoptosis pathway, specifically, through direct transcriptional regulation of the antiapoptotic gene BCL2 and indirect regulation of BCL-XL and MCL1.

Camila Bernal

Andrea Otalora

Alejandra Cañas

Alfonso Barreto

Karol Prieto

Martin Montecino

Adriana Rojas

Regulatory Role of the RUNX2 Transcription Factor in Lung Cancer Apoptosis

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and there is currently a lack of effective treatment options to control the metastasis. This study was performed to examine the mechanisms of the migration and invasion characteristics of HCC, with the aim of reducing metastasis by inhibiting cancer cell migration and invasion. In this study, we used Stellettin B, an active compound isolated from Stelletta sponges, as the experimental drug and evaluated its inhibition effects on cell migration and invasion in human hepatoma cells (HA22T and HepG2). MTT assay, gelatin zymography, and western blotting were employed. The results showed that Stellettin B significantly inhibited the protein expressions of MMP-2, MMP-9, and uPA, while upregulating the protein expressions of TIMP-1 and TIMP-2. The expressions of p-FAK, p-PI3K, p-AKT, p-mTOR, and MAPKs (p-JNK, p-JUN, p-MAPKp38, and p-ERK) were decreased with increasing concentrations of Stellettin B. Our results suggest that Stellettin B-dependent downregulation of MMP-2 and MMP-9 activities could be mediated by FAK/PI3K/AKT/mTOR and MAPKs signaling pathways in HA22T and HepG2 cells, preventing HCC invasion and migration.

Tsung-Chang Tsai

Wen-Tung Wu

Jen-Jie Lin

Jui-Hsin Su

Yu-Jen Wu

Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways

As many parts of the world continue to fight the innumerable waves of COVID-19 infection, SARS-CoV-2 continues to sculpt its antigenic determinants to enhance its virulence and evolvability. Several vaccines were developed and used around the world, and oral antiviral medications are being developed against SARS-CoV-2. However, studies showed that the virus is mutating in line with the antibody&#x2019;s neutralization escape; thus, new therapeutic alternatives are solicited. We hereby review the key role that miRNAs can play as epigenetic mediators of the cross-talk between SARS-CoV-2 and the host cells. The limitations resulting from the &#x201C;virus intelligence&#x201D; to escape and antagonize the host miRNAs as well as the possible mechanisms that could be used in the viral evasion strategies are discussed. Lastly, we suggest new therapeutic approaches based on viral miRNAs.

Leyla Tahrani Hardin

Nan Xiao

miRNAs: The Key Regulator of COVID-19 Disease

Spermatogonial stem cell (SSC) counterparts known as female germline stem cells (fGSCs) were found in the mammalian ovary in 2004. Although the existence of fGSCs in the mammalian postnatal ovary is still under controversy, fGSC discovery encourages investigators to better understand the various aspects of these cells. However, their existence is not accepted by all scientists in the field because isolation of fGSCs by fluorescent activated cell sorting (FACS) has not been reproducible. In this study, we used differential adhesion to isolate and enrich fGSCs from mouse and human ovaries and subsequently cultured them in vitro. fGSCs were able to proliferate in vitro and expressed germ cell-specific markers Vasa, Dazl, Blimp1, Fragilis, Stella, and Oct4, at the protein level. Moreover, mouse and human fGSCs were, respectively, cultured for more than four months and one month in culture. Both mouse and human fGSCs maintained the expression of germ cell-specific markers over these times. In vitro cultured fGSCs spontaneously produced oocyte-like cells (OLCs) which expressed oocyte-relevant markers. Our results demonstrated that differential adhesion allows reproducible isolation of fGSCs that are able to proliferate in vitro over time. This source of fGSCs can serve as a suitable material for studying mechanisms underlying female germ cell development and function.

Maryam Saber

Pouya Tavakol

Fereshteh Esfandiari

Isolation of Female Germline Stem Cells from Mouse and Human Ovaries by Differential Adhesion

Cancer is one of the diseases with the highest mortality rate today, with breast cancer being the second most common type among the Brazilian population. Due to its etiological complexity and inefficiency of treatments, studies have focused on new forms of treatment. Among these forms of treatment, hormonal therapy seems to be an excellent auxiliary mechanism in tumoricidal activity, and melatonin has great potential as a modulator of the immune system. Thus, the present study is aimed at evaluating the effect of the hormone melatonin on the coculture of colostrum polymorphonuclear cells and MCF-7 cancer cells and evaluates the effect of this hormone using a modified transport system. A feasibility analysis was performed by fluorescence microscopy at three cell incubation times, 2 hours, 24 hours, and 72 hours. The measurement of cytokines in the cell supernatant occurred in 24 hours, and the apoptosis assay was performed in 72 hours using flow cytometry. The results showed higher levels of cell viability in groups treated with melatonin and less viability in groups containing a coculture of polymorphonuclear cells and MCF-7 after 72 hours of incubation. Furthermore, the apoptosis and necrosis rates were higher in coculture polymorphonuclear and MCF-7 cells, especially in groups containing microemulsion as a modified release agent. These data suggest that melatonin, especially if associated with a modified release system, has immunomodulatory effects on human colostrum polymorphonuclear cells. These cells can play a crucial role in the resolution of the tumor through their mediation and inflammatory action.

Waynner O. Sousa

Mahmi Fujimori

Tassiane C. Morais

Milena B. Santos

Gabriel F. S. Rodrigues

Katleyn P. G. Silva

Andr&#x00E9; H. F. Torres

Adenilda C. Honorio-Fran&#x00E7;a

Eduardo L. Fran&#x00E7;a

Effects of Modified Melatonin Release on Human Colostrum Neutrophils to Induce Death in the MCF-7 Cell Line

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International Journal of Cell Biology publishes original research articles as well as review articles in all areas of cell biology.

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International Journal of Cell Biology publishes original research articles as well as review articles in all areas of cell biology.

International Journal of Cell Biology