Zha Yong, Yao Qian, Liu Jin-Sheng, Wang Yuan-Yuan, Sun Wei-Ming
Department of Gastroenterological Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
Oncol Lett. 2018 Nov;16(5):5709-5714. doi: 10.3892/ol.2018.9359. Epub 2018 Aug 23.
Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), and HBV X protein (HBx) serves an essential role in the development of HCC. However, its mechanism remains to be elucidated. The aim of the present study was to investigate the role and mechanism of the HBx protein in the epithelial-mesenchymal transition (EMT) and metastasis of HCC. The HCCLM3 cell line was transfected with a HBx-expressing vector. The effects of HBx overexpression on proliferation, migration, invasion and EMT capacities of the HCCLM3 cell line were evaluated using MTT, migration and invasion assays, and western blotting, respectively. Furthermore, the impact of High mobility group AT-hook 2 (HMGA2) knockdown on HBx-mediated metastasis was investigated in the HCC cell line HCCLM3. The results demonstrated that HBx significantly upregulated HMGA2 expression, and enhanced the proliferation, EMT, invasion and migration in HCC cells. Furthermore, HMGA2 knockdown almost abolished HBx-induced EMT and metastasis in HCC. The results of the present study suggest that HBx promotes the proliferation, EMT, invasion and migration of HCC cells by targeting HMGA2. HMGB2 may serve as a potential therapeutic target for HBV-associated HCC.
慢性乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）的主要危险因素，且HBV X蛋白（HBx）在HCC的发生发展中起重要作用。然而，其机制仍有待阐明。本研究旨在探讨HBx蛋白在HCC上皮-间质转化（EMT）及转移中的作用和机制。用表达HBx的载体转染HCCLM3细胞系。分别采用MTT法、迁移和侵袭实验及蛋白质印迹法评估HBx过表达对HCCLM3细胞系增殖、迁移、侵袭及EMT能力的影响。此外，在HCC细胞系HCCLM3中研究了高迁移率族AT钩蛋白2（HMGA2）敲低对HBx介导的转移的影响。结果表明，HBx显著上调HMGA2表达，并增强了HCC细胞的增殖、EMT、侵袭和迁移能力。此外，HMGA2敲低几乎消除了HBx诱导的HCC中的EMT和转移。本研究结果提示，HBx通过靶向HMGA2促进HCC细胞的增殖、EMT、侵袭和迁移。HMGB2可能作为HBV相关HCC的潜在治疗靶点。
