RNF185-AS1 promotes hepatocellular carcinoma progression through targeting miR-221-5p/integrin β5 axis

Life Sci. 2021 Feb 15:267:118928. doi: 10.1016/j.lfs.2020.118928. Epub 2020 Dec 31.

Abstract

Aims: Recently, long noncoding RNAs (lncRNAs) have been reported to play important role in the pathogenesis of various cancers. However, the functions of RNF185-AS1 in hepatocellular carcinoma (HCC) remain unknown.

Materials and methods: The RNF185-AS1 expression in HCC cells and tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of RNF185-AS1 on tumor cell proliferation, migration and invasion were assessed by Cell Counting Kit-8 (CCK8) assay, colony formation assay, transwell assay. The luciferase reporter assay, RNA-binding protein immunoprecipitation assay, qRT-PCR and Western blot were performed to explore and confirm the interaction between RNF185-AS1 and miR-221-5p and integrin β5. The role of RNF185-AS1 in tumor progression was explored through in vivo experiments.

Key findings: RNF185-AS1 was highly expressed in HCC tissues and cell lines. High levels of RNF185-AS1 were correlated with advanced TNM stage, distant metastasis and a poorer overall survival rate. RNF185-AS1 knockdown inhibited cell proliferation, migration and invasion. Additionally, RNF185-AS1 acted as a sponge for miR-221-5p and integrin β5 was identified as a target gene of miR-221-5p. Rescue assays showed that miR-221-5p inhibitor or integrin β5 overexpression rescued the function of RNF185-AS1 knockdown on cell proliferation, migration, and invasion. Moreover, we found that RNF185-AS1 knockdown inhibited tumor growth and metastasis.

Significance: Our study demonstrates that RNF185-AS1 is a new oncogenic lncRNA in HCC and suggests that the RNF185-AS1/miR-221-5p/integrin β5 axis might be a potential therapeutic target for HCC.

Keywords: Hepatocellular carcinoma; Integrin β5; RNF185-AS1; miR-221-5p.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Humans
  • Integrin beta Chains / genetics
  • Integrin beta Chains / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA-Binding Proteins / genetics
  • Signal Transduction
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Integrin beta Chains
  • MIRN221 microRNA, human
  • MicroRNAs
  • Mitochondrial Proteins
  • RNA, Antisense
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • integrin beta5
  • RNF185 protein, human
  • Ubiquitin-Protein Ligases