Suppressing circIDE/miR-19b-3p/RBMS1 axis exhibits promoting-tumour activity through upregulating GPX4 to diminish ferroptosis in hepatocellular carcinoma

Epigenetics. 2023 Dec;18(1):2192438. doi: 10.1080/15592294.2023.2192438.

Abstract

Ferroptosis is a newly characterized form of iron-dependent non-apoptotic cell death, which is closely associated with cancer progression. However, the functions and mechanisms in regulation of escaping from ferroptosis during hepatocellular carcinoma (HCC) progression remain unknown. In this study, we reported that the RNA binding motif single stranded interacting protein 1 (RBMS1) participated in HCC development,and functioned as a regulator of ferroptosis. Clinically, the downregulation of RBMS1 occurred in HCC tissues, and low RBMS1 expression was associated with worse HCC patients survival. Mechanistically, RBMS1 overexpression inhibited HCC cell growth by attenuating the expression of glutathione peroxidase 4 (GPX4)and further facilitated ferroptosis in vitro and in vivo. More importantly, a novel circIDE (hsa_circ_0000251) was identified to elevate RBMS1 expression via sponging miR-19b-3p in HCC cells. Collectively, our findings established circIDE/miR-19b-3p/RBMS1 axis as a regulator of ferroptosis, which could be a promising therapeutic target and prognostic factor.

Keywords: CircRNA; Ferroptosis; RNA binding protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA Methylation
  • DNA-Binding Proteins / genetics
  • Ferroptosis* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • RNA-Binding Proteins / genetics

Substances

  • RNA, Circular
  • MicroRNAs
  • RBMS1 protein, human
  • DNA-Binding Proteins
  • RNA-Binding Proteins

Grants and funding

This study was supported by grants from the China Postdoctoral Science Foundation Funded Project (2021M703685) and the Guiding Science and Technology Project of Ganzhou Science and Technology Bureau (GZ2020ZSF039).