Pivotal role of mir-34a in Prostate Cancer

Cancer is one main cause of death in the developed and developing countries, and itsprevalence likely is increasing in future. In Iran, cancer is appearing as a public healthproblem among a group of non-contagious diseases. Evidence shows prostate cancer is the5th most common cancer in the world and the 2nd major cause of death among men. In thepast several years, the importance of microRNAs and alteration in the expression in cancerhas been recognized. MicroRNAs are endogenous, noncoding, and small RNA molecules(18-22 nucleotides), that involved in regulating gene expression at the post- transcriptional level byaffecting the stability or suppressing the translation of target mRNAs. The aberrant expressionof some micro-RNAs has been observed in prostate cancer cell lines, xenografts, andclinical samples that have vital roles in the pathogenesis of PCa. The microRNA-34a is one ofthe most important regulators of tumor suppression network. Under- expression of thismolecule observed in prostate cancer and several types of cancers that prevent tumor growthby regulating a great number of genes involved in oncogenic signaling pathways. It also playscritical roles in cell cycle, differentiation and apoptosis by recruitment regulatory genes such asc-Met, c-Myc, Bcl2 and some signaling pathways like Notch, Wnt, AR. Review of severalstudies have confirmed miR-34a plays critical role in the various molecular mechanisms oftumor suppression by regulating a wide variety targets in prostate cancer development andmetastasis. For instance, miR-34a by suppression Wnt pathway and AR-signaling contributeto decreasing metastasis of PCa to bone and inhibiting the growth of PCa cells, respectively.Likewise, miR-34a elevates apoptosis and decreases growth and invasion of PCa cells byrepressing Notch signaling pathway. Emerging evidence suggest restoration of miR-34amimic and its collaboration with some anti-cancer drugs can inhibit tumor growth and enhancetreatment efficiency via inducing apoptosis and chemosensitization in several cancers.According to excellent role of miR-34a in control the expression of many different targets, themore precise recognition of its signaling pathways and molecular regulatory mechanisms inboth normal and cancer cells contributed to find ways to treat cancer, including prostate.

Keywords:

Mir-34a , Prostate Cancer , Signaling Pathways , Tumor Suppressor , Therapy