MiR-34a: A Key Small Molecule with Great Effects

Cancer remains the third leading cause of death in Iran after cardiovascular diseases androad accidents. MicroRNAs are short, non-coding RNAs which are involved in differentpathways like; cell growth, differentiation, development, haematopoiesis, and apoptosis.MiRs function either as oncogenes or as tumour suppressors and, overexpression ofoncomiRs and/or downregulation of tumour suppressor miRs can promote cancers. SomemiRs like; let7g and miR-34a show a loss of function in different cancer types and representtumour-suppressive effects. MiR-34a, a tumour suppressor miRNA, is silenced orsignificantly downregulated in major classes of human cancers like brain, colon, gastric, lung,neuroblastoma, pancreatic, and prostate cancers. Various genetic and epigeneticmechanisms can be involved in miR-34a deregulation. For example, its gene is located in afragile site that is often deleted in human cancers or, promoter hypermethylation of this miRhas been observed in some tumours. MiR-34a exerts its effects by regulateing numeroustarget genes that function in various cellular pathways. These genes include cyclin D1(CCND1), cyclin E2 (CCND2), cyclin dependent kinase 4 (CDK4), CDK6, CDC2, CDC25A,CDC25C, E2F transcription factor 1 (E2F1), E2F3, c-MYC, MYCN, silent informationregulator 1 (SIRT1), SURVIVIN, Kruppel-like factor 4 (KLF4), metastasis associated 1, familymember 2 (MTA2), yinyang1 (YY1), NOTCH1, C-Met, WNT1 and Lymphoid enhancerbindingfactor-1 (LEF1). Thus, miR-34a is involved in different biological processes such ascell-cycle arrest, induction of apoptosis and senescence-like phenotypes by regulating theexpression of these genes. There are several reports demonstrating that forced expression ofmiR-34a can induce apoptosis; inhibit cell proliferation, tumour growth and invasion; andmodulate sensivity of tumour cells to chemotherapeutic agents. Taken together, differentstudies demonstrated that miR-34a, may be considerd as a novel and potential diagnosticagents.

Keywords:

Cancer , Non-coding RNA , MiR34a , Downregulation , Biomarker