miR-335 inhibits the proliferation and invasion of clear cell renal cell carcinoma cells through direct suppression of BCL-W.

Increasing evidence has demonstrated that small non-coding microRNAs (miRNAs) play important roles in cancer development and progression. Recent studies have shown that microRNA-335 (miR-335) functions as an oncogene or a tumor suppressor in various human cancer types, but its role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. In our study, we firstly found that the expression level of miR-335 was significantly downregulated in ccRCC tissues versus corresponding non-tumor tissues and the low expression of miR-335 was significantly associated with lymph node metastasis, larger tumor size, and poor T stage. Then, we found that overexpression of miR-335 significantly suppressed the proliferation and invasion of 786-O and CaKi-1 ccRCC cell lines. We subsequently found that miR-335 could interact with the 3'-untranslated regions (3'UTR) of B-cell CLL/lymphoma 2 like 2 (BCL-W or BCL2L2) messenger RNA (mRNA) and repress its expression. In addition, re-expression of BCL-W (without the 3'UTR) could partially abrogate the miR-335-induced 786-O and CaKi-1 ccRCC cell proliferation and invasion inhibition. Furthermore, we found that expression patterns of miR-335 were inversely correlated with those of BCL-W mRNA in ccRCC tissues. Taken together, these results indicate that miR-335 acts as a novel tumor suppressor to regulate ccRCC cell proliferation and invasion through downregulation of BCL-W expression.