Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
Sci Rep. 2017 Jan 5;7:40089. doi: 10.1038/srep40089.
Hepatitis B virus X protein (HBx) is involved in the initiation and progression of hepatocellular carcinoma (HCC). However, the mechanism is still needed to be elucidated. In this study, we explored the relationship between HBx and microRNA and their roles in hepato-carcinogenesis. Firstly, by global microarray-based microRNA profiling and qRT-PCR, we found miR-181a was strongly up-regulated in HepG2.2.15 cells (HBV positive) and pHBV1.3-expressing HepG2 cells, and HBx played a major role in it. Secondly, reduced PTEN protein expression in the presence of HBx was aslo mediated by miR-181a, and in the Luciferase reporter system, miR-181a inhibited the PTEN translation by binding the PTEN 3'-untranslated-region (UTR), and PTEN protein was decreased when epigenetic expression of miR-181a and rescued by knocking down miR-181a. Finally, HBx interrupted the balance between apoptosis and proliferation, which contributed to the development of hepatocellular carcinoma, was also related to the interaction of miR-181a and PTEN. Taken together, we presented here a novel cross-talk between miR-181a and PTEN which was raised by HBx, and this shined a new line in HBV-related hepato-carcinogenesis.
乙型肝炎病毒 X 蛋白（HBx）参与肝细胞癌（HCC）的发生和发展。然而，其机制仍需阐明。在本研究中，我们探讨了 HBx 与 microRNA 之间的关系及其在肝癌发生中的作用。首先，通过基于全基因组 microRNA 谱和 qRT-PCR 的分析，我们发现 miR-181a 在 HepG2.2.15 细胞（HBV 阳性）和表达 pHBV1.3 的 HepG2 细胞中强烈上调，HBx 在其中起主要作用。其次，在存在 HBx 的情况下，PTEN 蛋白表达的减少也是由 miR-181a 介导的，在荧光素酶报告系统中，miR-181a 通过结合 PTEN 3'-非翻译区（UTR）抑制 PTEN 的翻译，而 miR-181a 的表观遗传表达减少，当敲低 miR-181a 时可恢复 PTEN 蛋白。最后，HBx 破坏了凋亡和增殖之间的平衡，这有助于肝细胞癌的发展，也与 miR-181a 和 PTEN 的相互作用有关。总之，我们在这里提出了一个新的观点，即 HBx 上调的 miR-181a 和 PTEN 之间存在一种新的相互作用，这为 HBV 相关的肝癌发生提供了一个新的研究方向。
