HBx-induced MiR-1269b in NF-κB dependent manner upregulates cell division cycle 40 homolog (CDC40) to promote proliferation and migration in hepatoma cells

Journal of Translational Medicine

Research

Guang-ling Zhang¹  Min Liu²  Hong-xia Fan²  Li-ping Shao²  Hua Tang²  Yi Zhang²  Xiao-xiao Kong²  Xin Li²  Yan-ru Lv³  Xiang-yang Nong³ 

[1] Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan City, Hebei Province, China;Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, 300070, Tianjin, China;Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, 300070, Tianjin, China;The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China;

关键词: HCC;    HBx;    NF-κB;    miR-1269b;    CDC40;   

DOI  :  10.1186/s12967-016-0949-y

 received in 2016-03-05, accepted in 2016-06-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundOccurrence and progression of hepatocellular carcinoma (HCC) are associated with hepatitis B virus (HBV) infection. miR-1269b is up-regulated in HCC cells and tissues. However, the regulation of miR-1269b expression by HBV and the mechanism underlying the oncogenic activity of miR-1269b in HCC are unclear.MethodsReverse transcription quantitative PCR (RT-qPCR) was used to measure the expression of miR-1269b and target genes in HCC tissues and cell lines. Western blot analysis was used to assess the expression of miR-1269b target genes and related proteins. Using luciferase reporter assays and EMSA, we identified the factors regulating the transcriptional level of miR-1269b. Colony formation, flow cytometry and cell migration assays were performed to evaluate the phenotypic changes caused by miR-1269b and its target in HCC cells.ResultsWe demonstrated that the expression levels of pre-miR-1269b and miR-1269b in HBV-positive HepG2.2.15 cells were dramatically increased compared with HBV-negative HepG2 cells. HBx was shown to facilitate translocation of NF-κB from the cytoplasm to the nucleus, and NF-κB binds to the promoter of miR-1269b to enhance its transcription. miR-1269b targets and up-regulates CDC40, a cell division cycle 40 homolog. CDC40 increases cell cycle progression, cell proliferation and migration. Rescue experiment indicated that CDC40 promotes malignancy induced by miR-1269b in HCC cells.ConclusionWe found that HBx activates NF-κB to promote the expression of miR1269b, which augments CDC40 expression, contributing to malignancy in HCC. Our findings provide insights into the mechanisms underlying HBV-induced hepatocarcinogenesis.

【 授权许可】

CC BY   
© The Author(s) 2016