Huang Chao-Yuan, Huang Xin-Ping, Zhu Ji-Ye, Chen Zhi-Gang, Li Xian-Jian, Zhang Xue-Hui, Huang Shan, He Jian-Bo, Lian Fang, Zhao Yin-Nong, Wu Guo-Bin
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Oncol Rep. 2015 Jun;33(6):2889-98. doi: 10.3892/or.2015.3936. Epub 2015 Apr 28.
microRNAs (miRNAs) are known to be involved in the pathogenesis of hepatocellular carcinoma (HCC). miR-128-3p was recently reported to be deregulated in several types of cancer. However, the biological function and potential mechanisms of miR-128-3p in HCC remain unknown. In the present study, we found that miR-128-3p was frequently downregulated in HCC tissues and cell lines by qRT-PCR analysis. Moreover, functional assays showed that overexpression of miR-128-3p markedly suppressed HCC cell proliferation by inducing G1 phase cell arrest and migration. Mechanistically, miR-128-3p was confirmed to regulate PIK3R1 (p85α) expression thereby suppressing phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation using qRT-PCR and western blot analysis. Furthermore, correlation analysis and Kaplan-Meier estimates revealed an inverse correlation between miR-128-3p and p85α as well as a shorter disease-free survival (DFS) period after HCC resection in patients with low miR-128-3p expression. Hence, we conclude that miR-128-3p, which is frequently downregulated in HCC, inhibits HCC progression by regulating PIK3R1 and PI3K/AKT activation, and is a prognostic marker for HCC patients.
已知微小RNA(miRNA)参与肝细胞癌(HCC)的发病机制。最近有报道称,miR-128-3p在几种癌症类型中表达失调。然而,miR-128-3p在肝癌中的生物学功能和潜在机制仍不清楚。在本研究中,通过qRT-PCR分析,我们发现miR-128-3p在肝癌组织和细胞系中经常下调。此外,功能分析表明,miR-128-3p的过表达通过诱导G1期细胞停滞和迁移显著抑制肝癌细胞增殖。机制上,使用qRT-PCR和蛋白质印迹分析证实,miR-128-3p通过调节PIK3R1(p85α)表达来抑制磷脂酰肌醇3激酶(PI3K)/AKT途径的激活。此外,相关性分析和Kaplan-Meier估计显示,miR-128-3p与p85α呈负相关,且miR-128-3p低表达的肝癌患者肝切除术后无病生存期(DFS)较短。因此,我们得出结论,在肝癌中经常下调的miR-128-3p通过调节PIK3R1和PI3K/AKT激活来抑制肝癌进展,并且是肝癌患者的一个预后标志物。