title: HBx promotes cell proliferation by disturbing the cross-talk between miR-181a and PTEN.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Gong
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006515:Hepatitis B virus / Q000472:pathogenicity*; D022781:Hepatocytes / Q000502:physiology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human