Long non-coding RNA FEZF1-AS1 promotes cell invasion and epithelial-mesenchymal transition through JAK2/STAT3 signaling pathway in human hepatocellular carcinoma

Biomed Pharmacother. 2018 Oct:106:134-141. doi: 10.1016/j.biopha.2018.05.116. Epub 2018 Jun 26.

Abstract

Long non-coding RNAs (lncRNAs) have emerged as key regulators in the development of hepatocellular carcinoma (HCC). In the present study, we explored the expression profile and biological role of lncRNA FEZF1-AS1 in HCC. We observed remarkable upregulation of FEZF1-AS1 in HCC tissues and cell lines, and high FEZF1-AS1 expression was correlated with aggressive phenotypes and poor prognosis of HCC patients. Furthermore, we found that FEZF1-AS1 knockdown markedly inhibited the proliferation of HCC cells by inducing cell cycle arrest. In addition, FEZF1-AS1 knockdown suppressed HCC tumor growth in vivo. Moreover, FEZF1-AS1 knockdown inhibited the migration and invasion of HCC cells through suppression of JAK2/STAT3 signaling-mediated epithelial-mesenchymal transition (EMT). In conclusion, the present study for the first time demonstrated that FEZF1-AS1 serves as an oncogenic lncRNA in human HCC and implicated FEZF1-AS1 as a valuable therapeutic target for HCC treatment.

Keywords: Cell cycle; Epithelial-mesenchymal transition; FEZF1-AS1; Hepatocellular carcinoma; JAK2/STAT3 signaling pathway.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / enzymology*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Checkpoints
  • Cell Movement*
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism*
  • Kaplan-Meier Estimate
  • Liver Neoplasms / enzymology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*
  • Time Factors
  • Tumor Burden

Substances

  • RNA, Long Noncoding
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • JAK2 protein, human
  • Janus Kinase 2