MicroRNA-30e-3p inhibits glioma development and promotes drug sensitivity to temozolomide treatment via targeting canopy FGF signaling regulator 2

Cell Cycle. 2021 Nov;20(22):2361-2371. doi: 10.1080/15384101.2021.1974789. Epub 2021 Oct 17.

Abstract

Glioma is one of the most aggressive malignancies in the central nervous system and the prognosis of glioma patients remains poor. In this study, we investigated the function of microRNA-30e-3p (miR-30e-3p) in glioma development and its regulatory role in drug-resistance to temozolomide (TMZ). We found that miR-30e-3p was downregulated in glioma tissues and cell lines. Ectopic expression of miR-30e-3p inhibited the growth of glioma cells and arrested cell cycle at G0/G1 phase. Canopy FGF signaling regulator 2 (CNPY2) was predicted as a direct target of miR-30e-3p by bioinformatics analysis. Luciferase reporter assay confirmed the interaction between miR-30e-3p and CNPY2. We also demonstrated that miR-30e-3p suppressed glioma xenograft tumor development invivo and the inhibition was abolished by CNPY2 overexpression. In addition, we showed that overexpression of miR-30e-3p enhanced the sensitivity of glioma cell to TMZ treatment. Glioma cells with miR-30e-3p overexpression had decreased cell proliferation and enhanced cell apoptosis upon TMZ treatment. Moreover, we revealed that miR-30e-3p modulated TMZ sensitivity of glioma cells via negatively regulating CNPY2. Taken together, our findings demonstrate that miR-30e-3p plays a critical role in glioma development and drug sensitivity to TMZ treatment via negatively regulating CNPY2 expression. The study suggests that miR-30e-3p/CNPY2 could be developed as a novel target to improve the glioma therapy.Abbreviations: miR-30e-3p, microRNA-30e-3p; TMZ, temozolomide; CNPY2, canopy FGF signaling regulator 2; 3'-UTR, 3' untranslated region; NC, negative control.

Keywords: Glioma; microRNA-30e-3p; temozolomide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Resistance, Neoplasm / genetics
  • Glioma* / drug therapy
  • Glioma* / genetics
  • Humans
  • MicroRNAs* / genetics
  • Temozolomide* / pharmacology

Substances

  • Adaptor Proteins, Signal Transducing
  • CNPY2 protein, human
  • MIRN30a microRNA, human
  • MicroRNAs
  • Temozolomide

Grants and funding

This study was supported by Key Research and Development Program of Shaanxi (Grant No. 2019SF-104) and NSFC (Grant No. 81602210, 81702487).