Knockdown of circ_0055412 promotes cisplatin sensitivity of glioma cells through modulation of CAPG and Wnt/β-catenin signaling pathway

CNS Neurosci Ther. 2022 Jun;28(6):884-896. doi: 10.1111/cns.13820. Epub 2022 Mar 25.

Abstract

Introduction: Glioma is the most frequent primary cerebral tumor in adults. Recent evidence has suggested that circular RNAs (circRNAs) are associated with the pathological processes in glioma. In our study, we aimed to investigate the function and mechanism of circ_CAPG (circ_0055412) in glioma.

Methods: Firstly, circ_0055412 expression was examined through RT-qPCR analysis. Loss-of-function assays and animal experiments were implemented to evaluate the role of circ_0055412 on cisplatin resistance of glioma cells. Moreover, mechanism assays were done to probe into the regulatory mechanism of circ_0055412 in glioma cells.

Results: Circ_0055412 was found to be notably upregulated in glioma cells. Moreover, depletion of circ_0055412 enhanced cisplatin sensitivity of glioma cells in vitro and in vivo. Moreover, circ_0055412 recruited eukaryotic translation initiation factor 4A3 (EIF4A3) protein to stabilize capping actin protein, gelsolin like (CAPG) mRNA. Furthermore, circ_0055412 served as a sponge for microRNA-330-3p (miR-330-3p) and regulated nuclear factor of activated T cells 3 (NFATC3) expression to activate the transcription of catenin beta 1 (CTNNB1), thus participating in the activation of Wnt/β-catenin signaling pathway.

Conclusion: Circ_0055412 contributed to cisplatin resistance of glioma cells via stabilizing CAPG mRNA and modulating Wnt/β-catenin signaling pathway. This finding might provide novel information for the treatment of glioma.

Keywords: CAPG; NFATC3; Wnt/β-catenin signaling pathway; circ_0055412; glioma.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cisplatin / metabolism
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Glioma* / drug therapy
  • Glioma* / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Messenger
  • Wnt Signaling Pathway / genetics
  • beta Catenin / metabolism

Substances

  • MicroRNAs
  • RNA, Messenger
  • beta Catenin
  • Cisplatin