DNA methylation-mediated repression of microRNA-410 promotes the growth of human glioma cells and triggers cell apoptosis through its interaction with STAT3

Sci Rep. 2024 Jan 18;14(1):1556. doi: 10.1038/s41598-024-51976-x.

Abstract

This study's purpose was to confirm the observed underexpression of miRNA-410 in glioma tissues and several glioma cells by Quantitative RT-PCR. Our findings suggest that epigenetic alterations occurring at the promoter region of miR-410 may be responsible for the reduced expression of miR-410 in glioma. The occurrence of DNA methylation in the miR-410 promoter was verified to be more prevalent through glioma tissues contrasted to adjacent non-tumor brain tissues through the utilization of methylation-specific PCR and CpG bisulfite sequencing sites in the miR-410 promoter region. Accordantly, miR-410 expression in glioma cell lines was observed to be significantly lesser in comparison to that of the human fetal glial cell line. In addition, it was demonstrated through gain- and loss-of-function investigations that miR-410 exerts significant regulation over cell growth, cell cycle development, and glioma cell apoptosis. The findings of the Luciferase reporter assay and western blot analysis indicate that miR-410 has a direct effect on the 3'-UTR of signal transducer and activator of transcription 3 (STAT3), thereby inhibiting its expression within glioma cells. Besides, our clinical investigation indicates a negative association between miR-410 expression and STAT3 within the glioma tissues of humans. In aggregate, the data provided in this investigation indicates that miR-410 is subjected to underexpression via DNA methylation. Furthermore, it has been observed to perform its function as a tumor suppressor in glioma cells through direct targeting of STAT3. The previously mentioned results could potentially have significant implications for the advancement of a new therapeutic approach for treating glioma.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA Methylation
  • Gene Expression Regulation, Neoplastic
  • Glioma* / pathology
  • Humans
  • MicroRNAs* / metabolism
  • STAT3 Transcription Factor / metabolism

Substances

  • STAT3 Transcription Factor
  • MicroRNAs
  • STAT3 protein, human
  • MIRN410 microRNA, human