4.7 Article

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

Journal

INTERNATIONAL JOURNAL OF CANCER
Volume 141, Issue 9, Pages 1867-1878

Publisher

WILEY
DOI: 10.1002/ijc.30853

Keywords

renal cell carcinoma; milt-766-3p; SF2; proliferation; ONA-methylation

Categories

Funding

  1. National Science Foundation of China [31570775, 81602216]
  2. Natural Science Foundation of Shanghai [167ZR1426500]
  3. Shanghai Pujiang Program [16PJD037]

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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.

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