MicroRNA-302b-3p Suppresses Cell Proliferation Through AKT Pathway by Targeting IGF-1R in Human Gastric Cancer

Abstract

Background/Aims: MiR-302b is a major microRNA found in human embryonic stem cells and induced pluripotent stem cells. However, its function in gastric cancer progression remains unclear. Methods: Quantitative reverse transcription-PCR was performed to detect the expression levels of miR-302b-3p in gastric cancer tissues. MTT, colony formation, and flow cytometer analyses were conducted to explore the function of miR-302b-3p in MKN-45/SGC-7901 cells. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-302b-3p. Western blotting and RNA interference were used to evaluate the expression of the AKT signaling pathway and determine the mechanisms underlying miR-302b-3p-induced anti-tumor effects. Results: MiR-302b-3p expression was decreased in gastric cancer tissues and cell lines. Enforced expression of miR-302b suppressed cell proliferation and cell cycle G1-S transition and induced apoptosis. IGF-1R was found to be a direct target of miR-302b-3p, and silencing of IGF-1R resulted in the same biological effects as those induced by miR-302b-3p overexpression in gastric cancer cells. Importantly, both overexpression of miR-302b-3p and silencing of IGF-1R decreased AKT phosphorylation, which modulated AKT related cell cycle regulators (cyclin A2, cyclin D1, CDK2, and CDk6) and apoptotic protein Bax/Bcl-2. Conclusion: These results indicate the tumor suppressor role of miR-302b-3p in the pathogenesis of gastric cancer.