Tripartite Motif Containing 52 (TRIM52) Promotes Cell Proliferation in Hepatitis B Virus-Associated Hepatocellular Carcinoma
Yi Zhang, Shan-Shan Wu, Xiao-Hua Chen, Zheng-Hao Tang, Yong-Sheng Yu, Guo-Qing Zang
Medical College of Soochow University, Suzhou, Jiangsu, China (mainland)
Med Sci Monit 2017; 23:5202-5210
Available online: 2017-11-01
Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). HBV X protein (HBx) plays a crucial role in the development of HCC. Moreover, many tripartite motif (TRIM) family proteins exert diverse biological functions in hepatocarcinogenesis. However, as a novel member of this family, the specific effect of TRIM52 is still largely obscure. In the present study, we investigated the expression and function of TRIM52 in HBV-associated HCC.
MATERIAL AND METHODS: Fluorescence quantitative polymerase chain reaction (FQ-PCR) was performed to detect the HBV DNA levels in the peripheral blood of HCC patients. Quantitative real-time PCR (qRT-PCR) and Western blot analysis were performed to detect the expression of TRIM52, HBx, and NF-κB p65. HBx-pcDNA3.1 and TRIM52-shRNA were used to induce HBx ectopic expression and TRIM52 silencing, respectively. Pyrrolidine dithiocarbamate (PDTC) was used to block the activation of NF-κB. Cell proliferation was detected using the Cell Counting Kit-8 (CCK-8) assay.
RESULTS: TRIM52 expression was up-regulated together with HBx in HBV-associated HCC tissues. Ectopic expression of HBx elevated TRIM52 expression in HepG2 cells. TRIM52 silencing repressed the proliferation of HepG2.2.15 cells. Moreover, NF-κB p65 expression was increased in HCC cell lines. Blocking NF-κB activation with PDTC suppressed TRIM52 expression and attenuated the viability of HepG2.2.15 cells.
CONCLUSIONS: These findings indicate that TRIM52 can promote cell proliferation and HBx may regulate TRIM52 expression via the NF-κB signaling pathway in HBV-associated HCC.
Keywords: Hepatitis B virus, Liver Neoplasms, NF-kappa B, Ubiquitin-Protein Ligases