miR-142-3p inhibits aerobic glycolysis and cell proliferation in hepatocellular carcinoma via targeting LDHA
miR-142-3p inhibits aerobic glycolysis and cell proliferation in hepatocellular carcinoma via targeting LDHA
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miR-142-3p通过靶向LDHA抑制肝细胞癌的有氧糖酵解和细胞增殖
DOI：
10.1016/j.bbrc.2018.01.112
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发表时间：
2018-02-12
影响因子：
3.1
通讯作者：
Wu, Dehua
中科院分区：
文献类型：
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作者：
Hua, Shengni;Liu, Chengdong;Wu, Dehua
即使在富氧的条件下，癌细胞也会上瘾地依赖糖酵解。然而，微小(Mi)RNA调节癌细胞有氧糖酵解的机制还不完全清楚。在这里，我们证明了miR-142-3p在肝细胞癌(肝细胞癌)中的表达低于邻近的非肿瘤标本，这在癌症基因组图谱(TCGA)肝细胞癌队列和基因表达总览(GEO)数据集中得到了证实。功能和通路分析表明miR-142-3p与代谢密切相关。正如预测的那样，miR-142-3p的过表达抑制了肝癌细胞的有氧糖酵解，从而抑制了细胞的增殖。我们从机理上确定了乳酸脱氢酶A(LDHA)是miR-142-3P的靶标，它是有氧糖酵解的重要催化酶之一。外源miR-142-3p的表达降低了SK-Hep-1和Huh7细胞LDHA的蛋白水平。双荧光素酶检测结果表明，miR-142-3p直接调控LDHA的表达。LDHA过表达逆转了MIR-142-3P诱导的有氧酵解和细胞增殖的抑制作用。综上所述，这些结果表明miR-142-3p可能通过靶向LDHA而在肝癌中发挥肿瘤抑制作用，为肝癌的治疗提供了新的治疗靶点。(C)2018 Elsevier Inc.保留所有权利。
Cancer cells are addictively dependent on glycolysis even in an oxygen-rich condition. However, the mechanism underlying micro (mi)RNA regulation of aerobic glycolysis in cancer cells has not been fully understood. Here, we demonstrated that the expression of miR-142-3p was lower in hepatocellular carcinoma (HCC) as compared to adjacent non-tumor samples, which was confirmed in The Cancer Genome Atlas (TCGA) HCC cohorts and Gene Expression Omnibus (GEO) datasets. Function and pathway analysis showed that miR-142-3p was most relevent with metabolism. As predicted, the overexpression of miR-142-3p inhibited aerobic glycolysis and thus proliferation of HCC cells. Mechanistically, we identified lactate dehydrogenase A (LDHA), one of the important catalyticase for aerobic glycolysis, as the target of miR-142-3p. Exogenous expression of miR-142-3p reduced the protein levels of LDHA in both SK-Hep-1 and Huh7 cells. Dual luciferase report assays showed the expression of LDHA was directly modulated by miR-142-3p. miR-142-3p-induced deduction of aerobic glycolysis and proliferation were reversed by LDHA overexpression. Taken together, these results indicate that miR-142-3p could act as a tumor suppressor in HCC by targeting LDHA, suggesting new therapeutic targets for HCC treatment. (C) 2018 Elsevier Inc. All rights reserved.