MicroRNA-142-5p Overexpression Inhibits Cell Growth and Induces Apoptosis by Regulating FOXO in Hepatocellular Carcinoma Cells.
MicroRNA-142-5p Overexpression Inhibits Cell Growth and Induces Apoptosis by Regulating FOXO in Hepatocellular Carcinoma Cells.
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DOI：
10.3727/096504016x14719078133366
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发表时间：
2017-01-02
影响因子：
3.1
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Lou K;Chen N;Li Z;Zhang B;Wang X;Chen Y;Xu H;Wang D;Wang H
microRNA（miR）-142-5p在肝细胞癌（HCC）中的异常表达已有报道。然而，关于miR-142- 5 p在HCC中的功能作用的信息很少。本研究旨在探讨miR-142- 5 p异常表达对肝癌细胞生长和凋亡的影响及其机制。用miR-142- 5 p模拟物、抑制剂或相应的阴性对照转染人HCC细胞系HepG 2和SMMC-7721细胞。然后分析细胞活力、细胞周期分布和细胞凋亡。此外，还测定了Forkhead box，O类（FOXO）1和3，Bcl-2相互作用的细胞死亡介质（Bim），半胱天冬酶原3和活化的半胱天冬酶3的蛋白表达。转染miR-142- 5 p抑制剂后，过表达FOXO 1和FOXO 3，再次检测细胞活力和细胞凋亡。在HepG 2和SMMC-7721细胞中，miR-142- 5 p过表达均显著降低了相对细胞活力（p < 0.05）。miR-142- 5 p过表达可显著阻断G1/S期细胞的增殖，并显著增加G 0/G1期细胞的比例。此外，结果显示，miR-142- 5 p过表达显著诱导细胞凋亡，并统计学地升高FOXO 1、FOXO 3、Bim、procaspase 3和活化的caspase 3的蛋白表达水平。然而，转染miR-142- 5 p抑制剂的细胞显示相反的结果。此外，miR-142- 5 p抑制剂对细胞活力和凋亡的影响被过表达的FOXO逆转。总之，我们的研究结果表明，miR-142- 5 p过表达通过抑制细胞生长和诱导细胞凋亡在HCC中显示出重要的保护作用。这些作用可能是通过调控肝癌细胞中FOXO的表达而实现的。
Abnormal expression of microRNA (miR)-142-5p has been reported in hepatocellular carcinoma (HCC). However, little information is available regarding the functional role of miR-142-5p in HCC. We aimed to explore the effects of miR-142-5p aberrant expression on HCC cell growth and cell apoptosis, as well as the underlying mechanism. Human HCC cell lines HepG2 and SMMC-7721 cells were transfected with miR-142-5p mimic, inhibitor, or a corresponding negative control. Cell viability, cell cycle distribution, and cell apoptosis were then analyzed. In addition, protein expression of Forkhead box, class O (FOXO) 1 and 3, a Bcl-2-interacting mediator of cell death (Bim), procaspase 3, and activated caspase 3 was measured. After transfection with miR-142-5p inhibitor, FOXO1 and FOXO3 were overexpressed, and then the cell viability and cell apoptosis were determined again. The relative cell viability in both HepG2 and SMMC-7721 cells was significantly reduced by miR-142-5p overexpression (p < 0.05). miR-142-5p overexpression displayed a significant blockage at the G1/S transition and significantly increased the percentages of G0/G1 phase. Moreover, the results showed that miR-142-5p overexpression significantly induced cell apoptosis and statistically elevated the protein expression levels of FOXO1, FOXO3, Bim, procaspase 3, and activated caspase 3. However, the cells transfected with miR-142-5p inhibitor showed contrary results. Additionally, the effects of miR-142-5p inhibitor on cell viability and apoptosis were reversed by overexpression of FOXO. In conclusion, our results suggest that miR-142-5p overexpression shows an important protective role in HCC by inhibiting cell growth and inducing apoptosis. These effects might be by regulating FOXO expression in HCC cells.