HBV triggers APOBEC2 expression through miR-122 regulation and affects the proliferation of liver cancer cells
HBV triggers APOBEC2 expression through miR-122 regulation and affects the proliferation of liver cancer cells
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HBV 通过 miR-122 调节触发 APOBEC2 表达并影响肝癌细胞的增殖。
DOI：
10.3892/ijo.2019.4870
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发表时间：
2019-11-01
影响因子：
5.2
通讯作者：
Zhang, Fengmin
中科院分区：
文献类型：
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作者：
Li, Aimei;Wu, Jing;Zhang, Fengmin
乙型肝炎病毒（HBV）感染导致全球50%的肝癌病例，该疾病是癌症相关死亡的主要原因之一。据报道，肝癌发生的一种潜在机制是肝细胞中载脂蛋白B mRNA编辑酶催化亚基2（APOBEC2）过表达诱导的肿瘤抑制基因发生突变。此外，已观察到HBV抑制肝细胞中微小RNA（miR）-122的表达；然而，肝癌发生所涉及的分子机制仍不清楚，需要进一步研究。在本研究中，对HBV感染在调节miR - 122和APOBEC2表达以及肝癌发生中的机制作用进行了研究。逆转录定量PCR和蛋白质印迹分析显示，HBV感染后APOBEC2表达显著上调。值得注意的是，APOBEC2在Huh7和HepG2肝癌细胞系中的表达谱与miR - 122相反；这种miR是肝脏中最丰富的微小RNA，并与肝癌发生有关。从机制上讲，通过双荧光素酶试验证明miR - 122能够特异性结合APOBEC2 mRNA的3' - 非翻译区（3' UTR），抑制其表达。总之，本研究的结果可能有助于深入了解HBV感染在调节miR - 122表达中的机制作用，miR - 122靶向APOBEC2 mRNA的3' UTR，进而诱导肝癌发生。
Hepatitis B virus (HBV) infection is responsible for 50% of liver cancer cases globally; this disease is one of the leading causes of cancer-associated mortality. One reported mechanism underlying the development of liver cancer is the mutation of tumor suppressor genes induced by the overexpression of apolipoprotein B mRNA-editing enzyme catalytic subunit 2 (APOBEC2) in hepatocytes. In addition, it has been observed that HBV inhibited microRNA (miR)-122 expression in hepatocytes; however, the molecular mechanisms involved in liver cancer development remain unknown and further investigations are required. In the present study, the mechanistic roles of HBV infection in modulating the expression of miR-122 and APOBEC2, and the development of liver cancer, were investigated. Reverse transcription-quantitative PCR and western blot analyses revealed that APOBEC2 expression was markedly upregulated following HBV infection. Of note, the expression profile of APOBEC2 in the Huh7 and HepG2 liver cancer cell lines opposed that of miR-122; this miR is the most abundant miRNA in the liver and has been associated with hepatocarcinogenesis. Mechanistically, it was demonstrated via a dual-luciferase assay that miR-122 could specifically bind to the 3 '-untranslated region (3 ' UTR) of APOBEC2 mRNA, inhibiting its expression. Collectively, the findings of the present study may provide insight into the mechanistic role of HBV infection in modulating the expression of miR-122, which targets the 3 ' UTR of APOBEC2 mRNA, subsequently inducing liver carcinogenesis.