Infectious Disease Department, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Zhengzhou 450052, Henan, China.
Department of Physical Examination, The Third People's Hospital of Henan Province, Zhengzhou 450006, Henan, China.
Biol Chem. 2018 May 24;399(6):611-619. doi: 10.1515/hsz-2018-0178.
Hepatitis B virus X protein (HBx) played a key role in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Emerging evidence has demonstrated that miR-181b and the inhibitor of growth protein 5 (ING5) participated in the pathophysiological process. However, the regulatory mechanism of HBx remained unknown. The expression of miR-181b and ING5 in HCC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell viability was determined using the MTT method following HCC cell lines transfection. The interaction between miR-181b and ING5 was assessed by luciferase reporter assay. The nude mice tumor model was well established to evaluate the role and biological functions of HBx on the progression of HBV-related HCC in vivo. MiR-181b was upregulated and ING5 was downregulated in HCC tissues and cell lines. As suggested by the results from in vitro and in vivo experiments, HBx downregulates the expression of the miR-181b target gene ING5, resulting in the promotion of HCC cell proliferation. HBx accelerates proliferation activity of HCC cells by increasing miR-181b expression via targeting ING5, thereby influencing the progression of HBV-related HCC.
乙型肝炎病毒 X 蛋白（HBx）在乙型肝炎病毒（HBV）相关肝细胞癌（HCC）的发展中起着关键作用。新出现的证据表明，miR-181b 和生长抑制蛋白 5（ING5）参与了病理生理过程。然而，HBx 的调节机制尚不清楚。使用实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测 HCC 组织和细胞系中 miR-181b 和 ING5 的表达。通过 MTT 法检测 HCC 细胞系转染后细胞活力。通过荧光素酶报告基因检测评估 miR-181b 和 ING5 之间的相互作用。建立裸鼠肿瘤模型，以评估 HBx 在体内 HBV 相关 HCC 进展中的作用和生物学功能。miR-181b 在 HCC 组织和细胞系中上调，ING5 下调。体外和体内实验结果表明，HBx 通过靶向 ING5 下调 miR-181b 靶基因 ING5 的表达，从而促进 HCC 细胞增殖。HBx 通过增加 miR-181b 的表达来加速 HCC 细胞的增殖活性，从而影响 HBV 相关 HCC 的进展。
