title: Long noncoding RNA lncTCF7, induced by IL-6/STAT3 transactivation, promotes hepatocellular carcinoma aggressiveness through epithelial-mesenchymal transition.
abstract: BACKGROUND
  Accumulating evidence suggests the pro-inflammatory cytokine interleukin-6 (IL-6) in tumor microenvironment may promote the development of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown.
  
  
  METHODS
  The expression and promoter activity of lncTCF7 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The function of the STAT3 binding site in the lncTCF7 promoter region was tested by luciferase reporter assay with nucleotide substitutions. The binding of STAT3 to the lncTCF7 promoter was confirmed by chromatin immunoprecipitation assay (CHIP) in vivo. The effects of decreasing STAT3 with small interference RNA and inhibiting STAT3 activation by small molecular inhibitor on lncTCF7 expression were also determined.
  
  
  RESULTS
  We demonstrate that IL-6 could induce lncTCF7 expression in a time- and dose-dependent manner, and we showed that IL-6 transcriptionally activated the expression of lncTCF7 in HCC cells by activating STAT3, a transcription activator which binds to promoter regions of lncTCF7. Furthermore, knocking-down STAT3 and inhibiting STAT3 activation reduced lncTCF7 expression. Importantly, RNA interference-based attenuation of lncTCF7 prevented IL-6-induced EMT and cell invasion.
  
  
  CONCLUSIONS
  Thus, these data provides evidence to the existence of an aberrant IL-6/STAT3/ lncTCF7 signaling axis that leads to HCC aggressiveness through EMT induction, which could be novel therapeutic targets in malignancies.
authors.affiliation: Department of Hepatobiliary Surgery, Taixing People's Hospital, Yangzhou University School of Medicine, 1 Changzheng Road, Jiangsu Province, 225400, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, Taixing People's Hospital, Yangzhou University School of Medicine, 1 Changzheng Road, Jiangsu Province, 225400, People's Republic of China. zhangjuntx@aliyun.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Taixing People's Hospital, Yangzhou University School of Medicine, 1 Changzheng Road, Jiangsu Province, 225400, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Hepatobiliary Surgery, Taixing People's Hospital, Yangzhou University School of Medicine, 1 Changzheng Road, Jiangsu Province, 225400, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yin
authors.affiliation: Department of Hepatobiliary Surgery, Taixing People's Hospital, Yangzhou University School of Medicine, 1 Changzheng Road, Jiangsu Province, 225400, People's Republic of China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary Surgery, Taixing People's Hospital, Yangzhou University School of Medicine, 1 Changzheng Road, Jiangsu Province, 225400, People's Republic of China.
authors.forename: Wencan
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Hepatobiliary Surgery, Taixing People's Hospital, Yangzhou University School of Medicine, 1 Changzheng Road, Jiangsu Province, 225400, People's Republic of China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics* / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics*; D051822:T Cell Transcription Factor 1 / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human