PURPOSE: Although microRNAs (miRNAs) have been revealed as crucial modulators of tumorigenesis, our understanding of their roles in renal cell carcinoma (RCC) is limited.
Here we sought to identify human miRNAs that act as key regulators of renal carcinogenesis.
EXPERIMENTAL DESIGN: We performed microarray-based miRNA profiling of clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-141 both in vitro and in vivo, which was the most significantly downregulated in ccRCC tissues.
RESULTS: 74 miRNAs were dysregulated in ccRCC compared with normal tissues. miR-141 was remarkably downregulated in 92.6% (63/68) ccRCC tissues and would serve as a promising biomarker for discriminating ccRCC from normal tissues with an AUC of 0.93. Overexpression of miR-141 robustly impaired ccRCC cell migratory and invasive properties and suppressed cell proliferation by arresting cells at G0/G1 phase in vitro and in human RCC orthotopic xenografts. Significantly, the anti-tumor activities of miR-141 were mediated by its reversal regulation of EphA2, which then relayed a signaling transduction cascade to attenuate the functions of focal adhesion kinase (FAK), AKT, and MMP2/9. In addition, a specific and inverse correlation between miR-141 and EphA2 expression was obtained in human ccRCC samples. Finally, miR-141 could be secreted from the ccRCC donor cells, and be taken up and function moderately in the ccRCC recipient cells.
CONCLUSIONS: miR-141 serves as a potential biomarker for discriminating ccRCC from normal tissues and a crucial suppressor of ccRCC cell proliferation and metastasis by modulating the EphA2/p-FAK/p-AKT/MMPs signaling cascade.
Written by:
Chen X, Wang X, Ruan A, Han W, Zhao Y, Lu X, Xiao P, Shi H, Wang R, Chen L, Chen S, Du Q, Yang H, Zhang X. Are you the author?
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.
Reference: Clin Cancer Res. 2014 Mar 19. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-13-3224
PubMed Abstract
PMID: 24647573
UroToday.com Renal Cancer Section
