Effect of miR-186 targeting E-cadherin on proliferation and metastasis of renal cell carcinoma

Abstract

Objective: To investigate the role of miR-186 in renal cell carcinoma (RCC) and its molecular mechanism of miR-186 targeting E-cadherin to inhibit cell proliferation and metastasis of RCC. Methods: A total of 40 RCC samples which were collected in Shanxi Provincial People's Hospital from January 2015 to January 2019 and four RCC cell lines were measured the expression of miR-186 by real-time quantitative polymerase chain reaction (qPCR). The effect of miR-186 overexpression on the proliferation, invasion, migration and apoptosis of 786-O cells were detected by cell counting kit-8(CCK-8), colony formation, wound healing and Transwell assay and flow cytometric analysis. The effect of miR-186 on the expression of epithelial-to-mesenchymal transition (EMT) related markers (E-cadherin, N-cadherin and Vimentin) was analyzed by Western blot, and the dual luciferase reporter was used to verify the miR-186 targeting E-cadherin. Results: There were 26 males and 14 females with an age of (58.4±9.2) years. miR-186 expression levels decreased significantly in RCC tissues and cells (tissues: 0.005 2±0.000 4 vs 0.015 5±0.001 5, P<0.001; cells: 0.334 3±0.025 1, 0.457 0±0.026 6, 0.229 8±0.011 0, 0.741 1±0.091 0 vs 1.000 0±0.085 2, all P<0.001). The expression of miR-186 had a negative correlation with tumor size (≥4 cm: 0.003 2±0.003 4 vs<4 cm: 0.008 4±0.007 2, P<0.001), TNM staging (≤Ⅱ: 0.007 8±0.005 8 vs>Ⅱ: 0.002 7±0.002 3, P=0.021) and Fuhrman grade (<Ⅱ: 0.008 8±0.006 3 vs ≥Ⅱ: 0.004 6±0.003 0, P<0.001). The overexpression of miR-186 significantly inhibited cell proliferation and metastasis, and induced cell apoptosis. delivered.miR-186 overexpression can retard tumor growth in nude mice. Luciferase assay showed that E-cadherin was a direct target gene of miR-186. Conclusion: miR-186 may affect EMT of RCC and inhibit the proliferation and metastasis of RCC by directly regulating E-cadherin.