MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1α regulation.
MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1α regulation.
复制标题
miR-186通过HIF-1α调节抑制胃癌有氧糖酵解。
DOI：
10.1038/oncsis.2016.35
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发表时间：
2016-05-09
期刊：
影响因子：
6.2
通讯作者：
Tian Z
中科院分区：
文献类型：
--
作者：
Liu L;Wang Y;Bai R;Yang K;Tian Z
在人类恶性肿瘤中，microRNAs的去调控已经被很好地记录下来，其中microRNA-186(miR-186)在一些癌症中具有抑制增殖的作用。在这里，我们证明了miR-186的低表达促进了胃癌的有氧糖酵解。MIR-186抑制缺氧诱导因子-1α(HIF-1α)诱导的胃癌细胞株MKN45和SGC7901的增殖。细胞糖酵解，包括细胞葡萄糖摄取、乳酸、ATP/ADP和NAD+/NADH比率，也被miR-186抑制。MiR-186对缺氧诱导因子-1α的负调控作用影响其下游靶点，包括程序性死亡配体1和两个糖酵解关键酶--己糖激酶2和血小板型磷酸果糖激酶。体内移植瘤实验证实了miR-186的抗肿瘤作用。结果表明，miR186/HIF-1α轴在胃癌中具有抗肿瘤作用。
Deregulation of microRNAs in human malignancies has been well documented, among which microRNA-186 (miR-186) has an antiproliferative role in some carcinomas. Here we demonstrate that low expression of miR-186 facilitates aerobic glycolysis in gastric cancer. MiR-186 suppresses cell proliferation induced by hypoxia inducible factor 1 alpha (HIF-1α) in gastric cancer cell lines MKN45 and SGC7901. Cellular glycolysis, including cellular glucose uptake, lactate, ATP/ADP and NAD+/NADH ratios, are also inhibited by miR-186. The negative regulation of miR-186 on HIF-1α effects its downstream targets, including programmed death ligand 1 and two glycolytic key enzymes, hexokinase 2 and platelet-type phosphofructokinase. The antioncogenic effects of miR-186 are proved by in vivo xenograft tumor experiment. The results demonstrate that the miR-186/HIF-1α axis has an antioncogenic role in gastric cancer.