TY  - EJOU
AU  - Jiang, Lixia 
AU  - Shi, Shaohua 
AU  - Shi, Qiaofa 
AU  - Zhang, Huijuan 
AU  - Xia, Yu 
AU  - Zhong, Tianyu 

TI  - MicroRNA-519d-3p Inhibits Proliferation and Promotes Apoptosis by Targeting HIF-2α in Cervical Cancer Under Hypoxic Conditions
T2  - Oncology Research

PY  - 2018
VL  - 26
IS  - 7
SN  - 1555-3906

AB  - HIF-2α 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-2α 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-2α expression in cervical cancer under 
hypoxic conditions. miRNAs regulating HIF-2α 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-2α by miR-519d-3p was evaluated by Western blot and luciferase reporter assays. Effects 
of miR-519d-3p and HIF-2α 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-2α 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-2α was a target of miR-519d-3p. Additionally, miR-519d-3p overexpression inhibited cell proliferation, arrested the cell cycle transition from the G1 stage to the S stage, and 
promoted cell apoptosis under hypoxic conditions in cervical cancer. HIF-2α 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-2α under hypoxic conditions.
KW  - MicroRNAs (miRNAs); Hypoxia-inducible factor-2α (HIF-2α); Cervical cancer; Cell hypoxia

DO  - 10.3727/096504018X15152056890500