DNA-methylation-mediated repression of miR-766-3p promotes cell proliferation via targeting SF2 expression in renal

Chen Chen1, Sheng Xue2,3, Jin Zhang4

  • 1Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, 200072, China.

Insights

Epigenetic silencing of miR-766-3p via methylation is observed in renal cell carcinoma (RCC). Restoring miR-766-3p inhibits RCC progression by targeting SF2, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Aberrant microRNA (miRNA) expression is implicated in human malignancies.
  • Identifying and validating altered miRNAs is crucial for understanding cancer.
  • Renal cell carcinoma (RCC) pathogenesis requires further elucidation.

Purpose of the Study:

  • To identify novel epigenetic regulation of miR-766-3p in RCC.
  • To investigate the biological function and clinical significance of miR-766-3p in RCC.
  • To explore the therapeutic potential of targeting the miR-766-3p/SF2 axis in RCC.

Main Methods:

  • Bisulfate analysis to assess DNA methylation of the miR-766-3p promoter.
  • Correlation analysis between miR-766-3p expression levels and clinical parameters in RCC patients.
  • In vitro experiments to determine the effect of miR-766-3p on cell-cycle progression and SF2 expression.
  • Analysis of SF2 protein levels and its association with patient survival in RCC cohorts.

Main Results:

  • The promoter of miR-766-3p is significantly methylated in RCC tissues.
  • Downregulation of miR-766-3p correlates with advanced clinical stage and poor prognosis in RCC patients.
  • Upregulation of miR-766-3p inhibits cell-cycle progression by targeting SF2 and the SF2/P-AKT/P-ERK pathway.
  • High SF2 expression, a novel oncoprotein in RCC, is associated with poor survival.

Conclusions:

  • Epigenetic silencing of miR-766-3p by promoter methylation is a key event in RCC.
  • The miR-766-3p/SF2 axis plays a critical role in RCC progression.
  • Targeting the miR-766-3p/SF2 axis presents a promising therapeutic strategy for RCC.

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