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| Genes involved in CRC | Gene functions and epigenetic changes |
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| APC | Adenomatosis polyposis coli | Tumour suppressor gene, antagonist of Wnt signaling pathway. |
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| MGMT | O-6-methylguanine-DNA methyltransferase | Involved in repairing DNA damage; silencing by hypermethylation correlates with G to A mutations in the K-RAS oncogene. |
| CDKN2A/P14 | Cyclin-dependent kinase inhibitor 2A, alternated reading frame | Tumour suppressor gene, involved in cell cycle regulation; its silencing by hypermethylation is associated with increased risk of CRC. |
| HLTF | Helicase-like transcription factor | This gene encodes for a chromatin remodelling factor. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. Its silencing could increase CRC risk. |
| hMLH1, hMLH2 | MutL homolog 1, 2 | DNA repair genes; their silencing, by hypermethylation is associated with MSI CRC. |
| CDKN2A/P16 | Cyclin-dependent kinase inhibitor 2A | Tumor suppressor gene that plays an important role in regulating the cell cycle; mutations or inactivation by hypermethylation in the CDKN2A gene are associated with increased risk of a wide range of cancers. |
| CDH13 | H-cadherin | It is a regulator of cellular adhesion-deadhesion processes, and its inactivation through hypermethylation contributes to the dissemination of cancer cells. |
| UNC5C | Unc-5 homolog C | UNC5C is one of the Netrin-1 receptors, has tumor-suppressor activity. The loss of UNC5C expression is particularly prominent in colorectal cancer. |
| DCC | Deleted in colorectal carcinoma | Encodes for a membrane-bound protein of the immunoglobulin-CAM family and may function as tumor suppressor gene which controls programmed cell death. DCC has been identified on a region of chromosome 18, which is deleted in 70% of colorectal cancer. |
| COX2 | Prostaglandineendoperoxide synthase 2 | Involved in inflammation and mitogenesis, tumour angiogenesis and metastasis. |
| HACE 1 | E3 ubiquitin ligase | HACE1 might act as a tumor suppressor in colorectal carcinomas and HACE1 methylation might present a malignant potential in colorectal cancer. |
| RASSF1A | Ras association (RalGDS/AF-6) domain family 1 | Suppressor protein involved in death receptor-dependent apoptosis and it is localized to microtubules. |
| RUNX3 | Runt-related transcription factor 3 | This gene encodes a member of the runt domain-containing family of transcription factors and can either activate or suppress transcription. It also interacts with other transcription factors. It functions as a tumor suppressor, and its silencing by hypermethylation could influence CRC risk. |
| SOCS1 | Suppressor of cytokine signaling 1 | SOCS1 is involved in negative regulation of cytokines that signal through the JAK/STAT3 pathway; its silencing by hypermethylation could influence CRC risk. |
| CHFR | Checkpoint with FHA and RING finger | CHFR functions as part of an early G2/M checkpoint. CHFR might act as a tumor suppressor and CHFR methylation might, therefore, be a particular phenomenon of early colorectal cancer. |
| ADAM23 | A disintegrin and metalloproteinase domain 23 | Members of this family are membrane-anchored proteins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions. ADAM23 may be downregulated by aberrant promoter hypermethylation during the progression of colorectal cancer. |
| DLEC1 | Deleted in lung and oesophageal cancer 1 | May act as a tumor suppressor by inhibiting cell proliferation and its silencing by hypermethylation correlates with CRC risk. |
| SERF1 | Secreted frizzled -related protein 1 | Epigenetic silencing of SFRP genes lead to aberrant activation of the Wnt pathway. |
| MYOD | Myogenic factor 3 | MyoD removes cells from the cell cycle (halt proliferation) by enhancing the transcription of p21. Its silencing could influence CRC risk. |
| P15 | Cyclin-dependent kinase inhibitor 2B | TIS gene is a tumor suppressor, which encodes a cyclin-dependent kinase inhibitor and it is positively regulated by transforming growth factor- (TGF-). hypermethylation of the P15 gene promoter, which should silence gene expression, correlates with CRC risk. |
| P73 | Tumor protein p73 | P73 maps to chromosome region 1p36.3, which is frequently deleted in a variety of solid tumors. Participates in the apoptotic response to DNA damage. May be a tumor suppressor protein, so its silencing by aberrant methylation correlates with CRC risk. |
| WT1 | Wilms tumor 1 | It has a tumor suppressor as well as an oncogenic role in tumor formation. Then aberrant methylation could influence CRC risk. |
| Cyclin A1 | Cyclin A1 | Binds to trascription factor E2F-1, p21, Rb family protein; aberrant methylation in this gene could influence CRC risk. |
| MINT | | Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. |
| RAR-b | Retinoic acid receptor beta | Tumor suppressor gene, mediates the growth inhibitory action of retinoic acid; its silencing by hypermethylation promotes tumour progression. |
| CDH5 | Chromodomain helicase DNA-binding protein 5 | Tumor suppressor gene involved in regulating chromatin architecture and in modifying chromatin structure in an ATP-dependent manner. |
| RGC-32 | Response gene to complement | RGC-32 regulate a group of genes involved in chromatin assembly. RGC-32 knockdown induced an increase in acetylation of histones H2B lysine 5 (H2BK5), H2BK15, H3K9, H3K18, and H4K8, a decreased expression of SIRT1 and trimethylation of histone H3K27. RGC-32 silencing is associated with chromatin remodeling and activation of cell cycle. |
| miRNA124a | | It could be repressed by CpG island hypermethylation, relative to normal tissue; it could so influence expression of oncogenic protein. |
| miR-34b/c, miR-9-1, miR-129-2 and R-137 | | Methylation of these genes was observed in CRC cell lines and in primary CRC tumour respect to normal mucosa. |
| miR-21 | | Alterated methylation could upregulate this microRNA in colorectal cancer, promoting invasion and metastasis. |
| miR-143 | | Down regulated in colon cancer; expression of K-RAS was found inversely correlated with this microRNA in vivo; miR-143 was inversely correlated with mRNA and the protein expression of DNMT3A in CRC. |
| miR135 | | Inversed association between this microRNA and the level of APC mRNA was observed in colorectal adenomas and carcinoma. |
| miR-34a | | miR-34a may act as a tumor suppressor by blocking SIRT1, thereby permitting increased p53 activity. By deacetylating p53, SIRT1 decreases the ability of p53 to promote cell cycle arrest. SIRT1 activity may increase the risk of cancer. MiR 34a silencing, by hypermethylation cannot inhibit SIRT1 activity. |
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