Price Institute of Surgical Research and Department of Surgery, University of Louisville, Louisville, KY, 40202, USA.
Mol Cell Biochem. 2018 Apr;441(1-2):89-98. doi: 10.1007/s11010-017-3176-9. Epub 2017 Sep 8.
Primary liver cancer (hepatocellular carcinoma, HCC) is a leading cause of cancer-related deaths, and alternative ways to treat this disease are urgently needed. In recent years, novel approaches to cancer treatment have been based on microRNAs, small non-coding RNA molecules that play a crucial role in cancer progression by regulating gene expression. Overexpression of some microRNAs has shown therapeutic potential, but whether or not this was the case for microRNA-203 (miR-203) in liver cancer was unknown. Therefore, the aim of this study was to investigate the effect of miR-203 overexpression in liver cancer and explore the related mechanisms. Liver cancer cells from the HepG2 and Hep3B cell lines were transfected with either miR-203 mimics or negative control RNA, and then the cells were subjected to cell viability, cell proliferation, and Western blotting assays. As a result of microRNA-203 overexpression, HepG2 and Hep3B cell viability and cell proliferation significantly declined. Furthermore, microRNA-203 overexpression led to inhibited expression of phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3)/protein kinase B (Akt), c-Jun, and p38 mitogen-activated protein kinases (p38 MAPK), and restored glycogen synthase kinase 3 (GSK 3) activity in HepG2 cells. Our results suggest that c-Jun, p38 MAPK, PIK3CA/Akt, and GSK3 signaling involved in the effect of miR-203 on the proliferation of HCC cells.
原发性肝癌（肝细胞癌，HCC）是癌症相关死亡的主要原因，迫切需要寻找治疗这种疾病的替代方法。近年来，癌症治疗的新方法基于 microRNAs，这是一类小的非编码 RNA 分子，通过调节基因表达在癌症进展中发挥关键作用。一些 microRNAs 的过表达显示出治疗潜力，但 microRNA-203（miR-203）在肝癌中是否如此还不得而知。因此，本研究旨在探讨 miR-203 过表达对肝癌的影响，并探讨相关机制。用 miR-203 模拟物或阴性对照 RNA 转染 HepG2 和 Hep3B 细胞系的肝癌细胞，然后进行细胞活力、细胞增殖和 Western blot 分析。miR-203 过表达导致 HepG2 和 Hep3B 细胞活力和细胞增殖显著下降。此外，miR-203 过表达导致磷脂酰肌醇-4,5-二磷酸 3-激酶（PI3K）/蛋白激酶 B（Akt）、c-Jun 和 p38 丝裂原活化蛋白激酶（p38 MAPK）表达受到抑制，并恢复 HepG2 细胞中糖原合酶激酶 3（GSK 3）的活性。我们的结果表明，c-Jun、p38 MAPK、PI3KCA/Akt 和 GSK3 信号通路参与了 miR-203 对 HCC 细胞增殖的影响。
