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

Int J Cancer. 2017 Nov 1;141(9):1867-1878. doi: 10.1002/ijc.30853. Epub 2017 Aug 8.

Abstract

Aberrant expression of microRNA (miRNA) emerges as an important role in a wide range of human malignances, and further identification as well as validation of the change of these endogenous non-protein-coding transcripts is warranted. Here, we identify a novel epigenetic regulation of miR-766-3p and investigate its biological function as well as clinical significance in renal cell carcinoma (RCC). Bisulfate analysis elucidates that the promoter of miR-766-3p is highly methylated in RCC tissues compared to non-tumorous tissues. Notably, the downregulation of miR-766-3p is obviously associated with clinical stage and worse prognosis in RCC patients. Upregulated miR-766-3p attenuates cell-cycle progression via targeting SF2 expression and additional SF2/P-AKT/P-ERK signaling pathway. Moreover, high level of SF2, as a novel oncoprotein in RCC, was significantly associated with poor survival in a large cohort of RCC specimens. Taken together, our study presents a road map for the prediction and validation of miR-766-3p/SF2 axis and thus imparts a therapeutic way for further RCC progression.

Keywords: DNA-methylation; SF2; miR-766-3p; proliferation; renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA Methylation / genetics*
  • Epigenesis, Genetic / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Serine-Arginine Splicing Factors / genetics*

Substances

  • MIRN766 microRNA, human
  • MicroRNAs
  • SRSF1 protein, human
  • Serine-Arginine Splicing Factors