Dysregulation of miR-514a-3p has been reported in multiple human malignancies. However, its biological function and molecular mechanisms in renal cell cancer (RCC) remain unclear. The aims of this study were to explore the role of miR-514a-3p and its potential mechanism in human RCC.
The expression level of miR-514a-3p was quantified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 20 cases of paired ccRCC and adjacent normal tissues and RCC cell lines. The role of miR-514a-3p in RCC cells was further evaluated by functional analyses. Western blot was applied to probe into the biological mechanism of miR-514a-3p in RCC cells.
The qRT-PCR results confirmed that miR-514a-3p was dramatically down-regulated in ccRCC specimens. Restoration of miR-514a-3p expression might distinctively suppress cell proliferation, viability, migration and invasion in comparison with negative control in RCC cells and negatively regulate the proteins related to epithelial-mesenchymal transition (EMT), such as E-Cadherin, N-Cadherin and Vimentin. Results of luciferase reporter assay and Western blot analysis identified that miR-514a-3p might inversely regulate the expression of epidermal growth factor receptor (EGFR) directly by binding to its 3'-untranslated region (3'-UTR) at the translational level. Further studies showed that the phenotypic changes of RCC cells caused by miR-514a-3p occurred through EGFR/MAPK/ERK pathway rather than PI3K/AKT signaling. Moreover, the inhibitory effect of miR-514a-3p was also confirmed in vivo study.
MiR-514a-3p is a novel tumor suppressor in ccRCC and potentially functions through EGFR/MAPK/ERK pathway.
American journal of translational research. 2017 Dec 15*** epublish ***
Xinwen Ke, Xing Zeng, Xian Wei, Yuanqing Shen, Jiahua Gan, Huake Tang, Zhiquan Hu
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430030, Hubei, China.