MicroRNA-519d-3p Inhibits Proliferation and Promotes Apoptosis by Targeting HIF-2α in Cervical Cancer Under Hypoxic Conditions

HIF-2 alpha knockdown inhibits proliferation, arrests the cell cycle, and promotes apoptosis and autophagy under hypoxic conditions in cervical cancer. However, the upstream regulatory mechanism of HIF-2 alpha expression is unclear. MicroRNAs (miRNAs) degrade target mRNAs by binding to the 3'-untranslated region of mRNAs. In this study, we investigated the role of miRNAs in the regulation of HIF-2 alpha expression in cervical cancer under hypoxic conditions. miRNAs regulating HIF-2 alpha expression were predicted using TargetScan and miRanda and were determined in cervical cancer under hypoxic conditions by qRT-PCR. Additionally, the targeted regulation of HIF-2 alpha by miR-519d-3p was evaluated by Western blot and luciferase reporter assays. Effects of miR-519d-3p and HIF-2 alpha on cell proliferation, cell cycle, and apoptosis were analyzed by CCK-8 and flow cytometry assays, respectively. miR-106a-5p, miR-17-5p, miR-519d-3p, miR-526b-3p, and miR-20b-5p are potentially regulatory miRNAs that bound to the HIF-2 alpha 3'-untranslated region as per TargetScan and miRanda predictions. Expression of the five miRNAs was inhibited in HeLa cells under hypoxic conditions compared to normoxic conditions, and the expression of miR-519d-3p was lower than that of other miRNAs. Luciferase reporter assays showed that HIF-2 alpha was a target of miR-519d-3p. Additionally, miR-519d-3p over-expression inhibited cell proliferation, arrested the cell cycle transition from the G(1) stage to the S stage, and promoted cell apoptosis under hypoxic conditions in cervical cancer. HIF-2 alpha overexpression partially reversed the effect of miR-519d-3p. In conclusion, miR-519d-3p overexpression suppressed proliferation, inhibited the cell cycle, and promoted apoptosis of HeLa cells by targeting HIF-2 alpha under hypoxic conditions.