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Oncotarget. 2016 Apr 12;7(15):20324-37. doi: 10.18632/oncotarget.7951.

miR-155 regulates the proliferation and invasion of clear cell renal cell carcinoma cells by targeting E2F2.

Gao Y1,2, Ma X1,2, Yao Y1,2, Li H1,2, Fan Y1,2, Zhang Y1,2, Zhao C1,2, Wang L1,2, Ma M1,2, Lei Z1,2, Zhang X1,2.

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Department of Urology, Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, 100853, P. R. China.
State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, 100853, P. R. China.


MicroRNAs (miRNAs) have emerged as critical modulators of carcinogenesis and tumor progression. In the present work, we sought to identify the biological function of miR-155 as well as its underlying mechanism in clear cell renal cell carcinoma (ccRCC). We examined the expression of miR-155 in clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-155 both in vitro and in vivo. The results of this analysis indicated that miR-155 activity was significantly upregulated in ccRCC tissues compared with the corresponding normal tissues. miR-155 was associated with ccRCC aggressiveness in both cell lines and clinical specimens, and a specific and inverse correlation between miR-155 and E2F2 expression was found in human ccRCC samples. Overexpression of miR-155 in 786-O cells decreased E2F2 expression while reduction of miR-155 by anti-miR-155 in ACHN cells elevated E2F2 expression. Re-expression of E2F2 in 786-O cells repressed the cell migration/invasion abilities elevated by miR-155, whereas knockdown of E2F2 in ACHN cells restored these cellular functions hampered by the miR-155 inhibitor. Using Western blot and luciferase reporter assays, we determined that E2F2 was a direct target of miR-155. Taken together, the in vitro and in vivo results demonstrate that miR-155 functions as a tumor-promoting miRNA by targeting E2F2 in ccRCC.


E2F2; clear cell renal cell carcinoma; miR-155; proliferation and invasion

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