circFBLIM1 act as a ceRNA to promote hepatocellular cancer progression by sponging miR-346

J Exp Clin Cancer Res. 2018 Jul 27;37(1):172. doi: 10.1186/s13046-018-0838-8.

Abstract

Backgroud: Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular cancer (HCC) is largely unknown.

Methods: We performed circRNA microarrays to identify circRNAs that are aberrantly expressed in HCC tissues. Expression levels of a significantly upregulated circRNA, circFBLIM1, was detected by quantitative real-time PCR (qRT-PCR) in HCC cell lines and tissues. Then, we examined the functions of circFBLIM1 in HCC by cell proliferation, apoptosis, invasion and mouse xenograft assay. In addition, luciferase assay and RNA immunoprecipitation (RIP) assay were used to explore the miRNA sponge function of circFBLIM1 in HCC.

Results: Microarray analysis and qRT-PCR verified a circRNA termed circFBLIM1 that was upregulated in HCC tissues and cell lines. Knockdown of circFBLIM1 inhibited proliferation, invasion and promoted apoptosis in HCC. Via luciferase reporter assays, circFBLIM1 and FBLIM1 were observed to directly bind to miR-346. Subsequent experiments showed that circFBLIM1 and FBLIM1 regulated the expression of each other by sponging miR-346.

Conclusions: Taken together, we conclude that circFBLIM1 may function as a competing endogenous RNA (ceRNA) to regulate FBLIM1 expression through sponging miR-346 to exert regulatory functions in HCC. circFBLIM1 may be a diagnostic biomarker and potential target for HCC therapy.

Keywords: Circular RNAs; Competitive endogenous RNAs; FBLIM1; Hepatocellular cancer; miR-346.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics*
  • Disease Progression
  • Female
  • Heterografts
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microarray Analysis
  • RNA / biosynthesis
  • RNA / genetics
  • RNA / metabolism*
  • RNA, Circular
  • Transfection

Substances

  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • FBLIM1 protein, human
  • MIRN346 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA