MiR-449a Regulates Proliferation and Chemosensitivity to Cisplatin by Targeting Cyclin D1 and BCL2 in SGC7901 Cells

Abstract

Recently, several miRNAs have been determined as tumor suppressors in various cancers, such as microRNA-449a. However, the exact molecular mechanisms underlying miR-449a regulated cell proliferation and chemosensitivity in gastric cancer cells have not been well documented. The present study was designed to test whether miR-449a mediates cell proliferation and chemosensitivity in gastric cancer cells via regulating cyclin D1 and BCL2. In vitro, the ability of cell proliferation and cell viability were measured by MTT assay; cell cycle and cell apoptosis was detected by FCM. qRT-PCR was used to measure the expression of miR-449a. Western blot and real-time PCR assays were used to detect the expression of cyclin D1 and BCL2 in gastric cancer cell line SGC7901. miR-449a expression was downregulated in gastric cancer cell line SGC7901 and human gastric cancer tissues, compared to the gastric epithelial cell line GES-1 and matched non-tumor associated tissues. Upregulation of miR-449a reduced the proliferation of SGC7901 cells. Ectopic expression of miR-449a decreased the percentage of S phase cells, increased the percentage of G1/G0 phase cells and increased the apoptosis induced by cisplatin. Moreover, miR-449a inhibited SGC7901 cells proliferation and enhanced cisplatin chemosensitivity by downregulating expression of BCL2 and cyclin D1, respectively, via directly targeting the 3'-untranslated regions of BCL2 and cyclin D1 mRNA. This is the first report to provide evidence that miR-449a could modulate cell cycle and apoptosis through regulating cyclin D1 and BCL2 expression in SGC7901 cells.