Hu Junwei, Wang Zeyu, Wang Jinjun, Jian Yicheng, Dai Jiarun, Wang Xiaoping, Xiong Wujun
Department of Gastroenterology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, People's Republic of China.
Department of Digestive Endoscopy, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, People's Republic of China.
Onco Targets Ther. 2020 Sep 16;13:9159-9167. doi: 10.2147/OTT.S258251. eCollection 2020.
Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the third greatest cause of cancer-related death worldwide. Programmed cell death 4 (PDCD4) was reported as a potential tumor-suppressor in hepatocarcinogenesis. However, relatively little is known about mechanisms that regulate PDCD4 expression in HCC. The aim of the present study is to investigate the expression of PDCD4 and miR-182 in human HCC cell lines and clinical HCC specimens and determine whether PDCD4 is a direct target of miR-182 in HCC cell lines.
The expression of miR-182 and PDCD4 in human HCC cell lines and HCC tissues were examined using qRT-PCR and Western blot method. Transwell and wound healing assays were carried out to explore the influence of miR-182 on hepatoma cells migration. A luciferase reporter assay was conducted to confirm target association.
In our research, we found that PDCD4 was downregulated, whereas miR-182 was upregulated in liver cancer cell lines and HCC tissues. Transwell and wound healing assays illustrated that miR-182 contributed to migration activities of liver cancer cell lines. Loss or increase of miR-182 can lead to a negative expression of PDCD4 protein level. The luciferase reporter assay showed that PDCD4 is a direct target of miR-182.
All these findings suggest that miR-182 may act as an oncogenic role in liver cancer cells by directly and negatively regulating expression of PDCD4.
肝细胞癌（HCC）是最常见的原发性肝肿瘤，也是全球癌症相关死亡的第三大原因。程序性细胞死亡4（PDCD4）被报道为肝癌发生过程中的一种潜在肿瘤抑制因子。然而，关于肝癌中调节PDCD4表达的机制相对知之甚少。本研究的目的是调查人肝癌细胞系和临床肝癌标本中PDCD4和miR-182的表达，并确定PDCD4是否是肝癌细胞系中miR-182的直接靶点。
采用qRT-PCR和蛋白质印迹法检测人肝癌细胞系和肝癌组织中miR-182和PDCD4的表达。进行Transwell和伤口愈合试验以探讨miR-182对肝癌细胞迁移的影响。进行荧光素酶报告基因检测以确认靶点关联。
在我们的研究中，我们发现肝癌细胞系和肝癌组织中PDCD4表达下调，而miR-182表达上调。Transwell和伤口愈合试验表明，miR-182促进了肝癌细胞系的迁移活性。miR-182的缺失或增加可导致PDCD4蛋白水平的阴性表达。荧光素酶报告基因检测表明，PDCD4是miR-182的直接靶点。
所有这些发现表明，miR-182可能通过直接负向调节PDCD4的表达在肝癌细胞中发挥致癌作用。
