MicroRNA-181a promotes cell proliferation and inhibits apoptosis in gastric cancer by targeting RASSF1A

MicroRNA (miR)-181a is a member of the miR-181 family that serves a key role in the pathogenesis of various cancer types. The present study aimed to investigate the interaction between miR-181a and Ras association domain family protein1 isoform A (RASSF1A), and their roles in gastric carcinogenesis. The interaction between miR-181a and RASSF1A was assessed in cell lines and cancer tissues. The direct binding of miR-181a and RASSF1A was identified using a luciferase reporting gene system. The effects of miR-181a and RASSF1A on gastric cancer cell growth, cell cycle and apoptosis were assessed with a Cell Counting Kit-8 assay and flow cytometry. The effects of miR-181a on cell division cycle 25A (CDC25A), cyclin A2, cyclin D1, p21, Bcl-2-associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) protein levels were assessed in gastric cancer cell lines. miR-181a directly interacted with the 3′-untranslated region of RASSF1A and downregulated RASSF1A protein expression. In tissues from patients with gastric cancer, the miR-181a level was significantly higher in the tumor tissues and was negatively correlated with the RASSF1A protein level. RASSF1A suppressed gastric cancer cell proliferation and G1/S transition, and promoted apoptosis; whereas miR-181a promoted cancer cell proliferation and G1/S transition, and suppressed apoptosis. RASSF1A knockdown attenuated the effects of miR-181a downregulation on cell proliferation and apoptosis. Furthermore, miR-181a upregulated CDC25A, cyclin A2 and Bcl-2, and downregulated Bax protein expression in gastric cancer cell lines. These data indicate that miR-181a promotes gastric carcinogenesis, possibly through a direct interaction with RASSF1A.