Circ_SNX27 regulates hepatocellular carcinoma development via miR-637/FGFR1 axis

Environ Toxicol. 2022 Dec;37(12):2832-2843. doi: 10.1002/tox.23640. Epub 2022 Aug 27.

Abstract

Background: Circular RNAs (circRNAs) serve as critical regulatory factors in cancer development. Nonetheless, the potential regulatory mechanism of circRNA sorting nexin 27 (circ_SNX27) in hepatocellular carcinoma (HCC) is still unknown.

Methods: The circ_SNX27, microRNA-637 (miR-637), and fibroblast growth factor receptor 1 (FGFR1) levels were quantified by quantitative real-time polymerase chain reaction and western blot analysis. Next, function experiments were conducted using in vitro assays and in vivo senograft study. The relationship between miR-637 with circ_SNX27 or FGFR1 was uncovered by dual-luciferase reporter and RNA pull-down assays.

Results: The circ_SNX27 and FGFR1 levels were up-regulated, but miR-637 content was reduced in HCC. Circ_SNX27 down-regulation inhibited HCC cell proliferation, motility, and invasion and promoted apoptosis in vitro, as well as weakened tumor growth in vivo. Circ_SNX27 served as a sponge of miR-637 to promote FGFR1 expression. MiR-637 reduction abolished the restrained effect of circ_SNX27 absence on HCC cell development. Moreover, miR-637 curbed HCC cell malignant phenotype by regulating FGFR1.

Conclusion: Circ_SNX27 contributed to HCC development via miR-637/FGFR1 axis, offering a new idea for the treatment of HCC.

Keywords: FGFR1; circ_SNX27; hepatocellular carcinoma; miR-637.

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Sorting Nexins / genetics
  • Sorting Nexins / metabolism

Substances

  • Receptor, Fibroblast Growth Factor, Type 1
  • MicroRNAs
  • RNA, Circular
  • FGFR1 protein, human
  • SNX27 protein, human
  • Sorting Nexins
  • MIRN637 microRNA, human