MiR-216a, a tumor-related microRNA (miRNA), has been reported to be implicated in the tumorigenesis and progression of diverse types of human malignancies; however, its role in renal cell carcinoma (RCC) remains unclear. This study aimed to explore the biological role of miR-216a in RCC and clarify the potential mechanisms involved. In the present study, miR-216a was found to be significantly down-regulated in both RCC tissues and cell lines. Functional studies demonstrated that enhanced expression of miR-216a suppressed RCC cell proliferation, migration and invasion in vitro, inhibited tumor growth in vivo, and induced RCC cell cycle arrest and apoptosis. Moreover, the tumor-suppressing effects of miR-216a in RCC were abrogated by the miR-216a inhibitor treatment. Notably, toll-like receptor 4 (TLR4) was downregulated by miR-216a via direct binding to its 3' untranslated region in RCC cells. Furthermore, TLR4 expression was discovered to be markedly up-regulated and inversely correlated with miR-216a expression in RCC tissues. Mechanistic studies revealed that restoring the expression of TLR-4 alleviated miR-216a-induced inhibitory effects on proliferation, migration and invasion of RCC cells. Taken together, these findings suggest that miR-216a functions as a tumor suppressor in RCC by directly targeting TLR4 and that miR-216a might be a novel therapeutic target for RCC.
Keywords: Renal cell carcinoma; TLR4; miR-216a; tumor-suppressing.