Circular RNA hsa_circRNA_103809 promoted hepatocellular carcinoma development by regulating miR-377-3p/FGFR1/ERK axis

J Cell Physiol. 2020 Feb;235(2):1733-1745. doi: 10.1002/jcp.29092. Epub 2019 Jul 17.

Abstract

In the last decade, circular RNAs (circRNAs) emerge as important regulators in multiple biological processes. Lately, it is reported hsa_circRNA_103809 could play vital parts in several types of cancers. Based on the analysis of GEO data (GSE97332), hsa_circRNA_103809 was found to be dysregulated in hepatocellular carcinoma (HCC). However, the biological function and underlying regulatory mechanisms of hsa_circRNA_103809 in HCC remain unclear. Our results suggested that hsa_circRNA_103809 was overexpressed in HCC patients, and hsa_circRNA_103809 knockdown remarkably inhibited the proliferation, cycle progression, and migration of HCC cells. The investigations of molecular showed that hsa_circRNA_103809 could elevate the protein expression of a miR-377-3p target, fibroblast growth factor receptor 1 (FGFR1), through interacting with miR-377-3p and decreasing its expression level. Additionally, in vivo assays revealed hsa_circRNA_103809 short hairpin RNA served as a tumor suppressor through downregulating FGFR1 in HCC. This study systematically investigated novel regulatory signaling of hsa_circRNA_103809/miR-377-3p/FGFR1 axis, providing insights into hepatocellular carcinoma treatment from bench to clinic.

Keywords: FGFR1; cell cycle; cell migration; cell proliferation; hepatocellular carcinoma; hsa_circRNA_103809; miR-377-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology*
  • MAP Kinase Signaling System / genetics
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • RNA, Circular / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Signal Transduction / genetics*

Substances

  • MIRN377 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1