Circular RNA circFBXO11 modulates hepatocellular carcinoma progress and oxaliplatin resistance through miR-605/FOXO3/ABCB1 axis

J Cell Mol Med. 2020 May;24(9):5152-5161. doi: 10.1111/jcmm.15162. Epub 2020 Mar 28.

Abstract

Increasing findings suggest the critical role of circular RNA (circRNA) in human cancer, and chemotherapy resistance is a poor prognostic factor for hepatocellular carcinoma (HCC). The function of circRNA in the HCC oxaliplatin (OXA) resistance remains largely unknown. In this study, we found that circRNA circFBXO11 was significantly up-regulated in HCC tissues, and the circFBXO11 overexpression was associated with poor prognosis. CircFBXO11 was found to promote the HCC proliferation, cycle progress and OXA resistance. Mechanistically, circFBXO11 was predominantly localized in the cytoplasm and harboured the miR-605, thereby targeting FOXO3 protein. Furthermore, FOXO3 targeted the promoter region of ABCB1 to accelerate its expression. In conclusion, this research reveals the role of circFBXO11/miR-605/FOXO3/ABCB1 axis in the HCC OXA resistance, providing new insight for circRNA-based diagnostic and therapeutic strategies.

Keywords: ABCB1; FOXO3; circular RNA; hepatocellular carcinoma; oxaliplatin resistance.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Forkhead Box Protein O3 / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oxaliplatin / pharmacology
  • Oxaliplatin / therapeutic use*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Transcription, Genetic / drug effects

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN605 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Oxaliplatin