Evaluation the effect of 5-Aza Epi-drug on expression levels of pro-apoptotic miRNA-15 and miRNA-16 and Bcl2 gene target in human gastric carcinoma AGS cells

Introduction: In mammals, the Bcl-2 family can be divided into two subfamilies: the anti-apoptotic protein family, including Bcl-2, and the pro-apoptotic protein family, including Bax. The balance between antiapoptotic and pro-apoptotic members regulates the fate of the cell. The Bcl-2 protein is a key regulator of apoptosis and is also complicated in DNA repair, cell cycle and differentiation control. Certain its fundamental importance for the cellular fate, Bcl-2 expression is finely tuned by a variety of environmental and endogenous stimuli and regulated at both transcriptional and post-transcriptional levels. DNA methylation is somewhat dynamic and responsive to environmental conditions. Thus, several nongenotoxic Epi-drug have been found to affect gene function through changes in DNA methylation. For example, 5-Aza, as a chemical analogue of the nucleoside cytosine induces global hypomethylation. microRNAs are a group of regulatory RNAs that involved in post-transcriptional gene regulation. It has been shown that miR-15 induce apoptosis by targeting BCL2 and both microRNAs negatively regulate Bcl- 2 at a post-transcriptional level in several cancer. But whether 5-aza can influence miR-15 expression in AGS cells as human gastric carcinoma is not clear.Methods: The study was performed on in human gastric carcinoma AGS cells. Cells were treated with 5- aza. Relative expression levels of miRNA-15 and Bcl-2 examined, using quantitative RT-PCR. Treatment Results: We evaluate the miR-15 and Bcl-2 expression in AGS cell line. The Level of miR-15 are inversely correlated with BCL2 Expression in AGS. Thus, in AGS cell line we observed a concordant downregulationof miR-15 and overexpression of Bcl-2 mRNA transcript. The Epidrugs such as 5-aza can downregulated Bcl-2 expression. Conclusion: It recent results proposed that use of Epi-drug such as 5-aza can down-regulated Bcl-2 and can served as medication to reduce cell proliferation and subsequent metastasis in gastric carcinoma

Keywords:

AGS , miR-15 , Bcl-2 , 5-Aza