Lu Sen, Wu Jindao, Gao Yuanyuan, Han Guoyong, Ding Wenzhou, Huang Xinli
Department of Liver Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, PR China.
Department of General Surgery, Changzhou No.2 People's Hospital, Changzhou, Jiangsu Province 213000, PR China.
Int J Biol Macromol. 2016 May;86:43-9. doi: 10.1016/j.ijbiomac.2016.01.019. Epub 2016 Jan 8.
microRNAs (miRNAs) were known as transcriptional regulators to regulate the repertoires of target genes during the development of hepatocellular carcinoma (HCC). In this study, we investigated the roles of miR-4262 in the process of HCC. Our results showed that miR-4262 is overexpressed in HCC tissues and hepatoma cell lines (HepG2 and Sk-hep-1). We also found that miR-4262 enhanced the process of cell cycle and inhibited the apoptosis leading to promoted cell proliferation and activity. Moreover, the 3'UTR of PDCD4 was complementary to miR-4262 seed region and we confirmed that PDCD4 is the direct target of miR-4262 with 3'UTR luciferase assay. qPCR and WB analysis revealed that the level of PDCD4 was negatively correlated with the expression of miR-4262 in HepG2 cells. Furthermore, our results demonstrated that miR-4262-promoted cell proliferation was mediated by PDCD4 and miR-4262 can activate the NF-κB pathway to promote the accumulation of nuclear NF-κB/P65. All of these findings suggested miR-4262 may play a role in the development of HCC.
微小RNA（miRNA）作为转录调节因子，在肝细胞癌（HCC）的发展过程中调节靶基因库。在本研究中，我们调查了miR-4262在HCC进程中的作用。我们的结果显示，miR-4262在HCC组织和肝癌细胞系（HepG2和Sk-hep-1）中过表达。我们还发现，miR-4262增强了细胞周期进程并抑制了细胞凋亡，导致细胞增殖和活性增加。此外，PDCD4的3'UTR与miR-4262种子区域互补，我们通过3'UTR荧光素酶检测证实PDCD4是miR-4262的直接靶标。qPCR和WB分析显示，HepG2细胞中PDCD4的水平与miR-4262的表达呈负相关。此外，我们的结果表明，miR-4262促进的细胞增殖由PDCD4介导，并且miR-4262可以激活NF-κB途径以促进核NF-κB/P65的积累。所有这些发现表明，miR-4262可能在HCC的发展中发挥作用。
