title: HBx-induced MiR-1269b in NF-κB dependent manner upregulates cell division cycle 40 homolog (CDC40) to promote proliferation and migration in hepatoma cells.
abstract: Occurrence 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.
  
  
  
  Reverse 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.
  
  
  
  We 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.
  
  
  
  We 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.
authors.affiliation: Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Kong
authors.affiliation: Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070, China.|The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Lv
authors.affiliation: Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Shao
authors.affiliation: Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070, China.|The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China.
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Nong
authors.affiliation: 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.
authors.forename: Guang-Ling
authors.initials: GL
authors.lastname: Zhang
authors.affiliation: Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070, China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Fan
authors.affiliation: Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Tianjin Life Science Research Center, School of Basic Medical Sciences, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Tianjin, 300070, China. htang2002@yahoo.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D000072260:RNA Splicing Factors / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D020413:3' Untranslated Regions; C112200:CDC40 protein, human; D018797:Cell Cycle Proteins; C000600169:MIRN1269 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D000072260:RNA Splicing Factors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: CDC40; HBx; HCC; NF-κB; miR-1269b