miRNA-133b and miRNA-135a induce apoptosis via the JAK2/STAT3 signaling pathway in human renal carcinoma cells

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• 作者：Wenbin Zhou^a ; Xingjie Bi^b ; Guojun Gao^c ; Lijiang Sun^d ; ^{sunljiangqd@sina.com}
• 关键词：miR-133b ; miR-135a ; ccRCCs ; JAK2 ; STAT3 ; Apoptosis
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：84
• 期：Complete
• 页码：722-729
• 全文大小：2082 K
• 卷排序：84

文摘

Aberrantly expressed microRNAs (miRNAs) are involved in many diseases including cancer. In clear cell renal cell carcinoma (ccRCCs) expression of miR-133b and miR-135a is reduced compared to control tissue and other sarcomas but the functional effects of this downregulation are not fully understood. This study aimed at evaluating the miR-133b and miR-135a expression profiles in different RCC subtypes and the functional role of these miRNAs. Viability and apoptosis were examined in three different ccRCC cell lines (786-O, A498 and SN12-PM6) after over-expression of these miRNAs. The modulation of JAK2 and the JAK2/STAT3 pathways was determined by Western blot. Transient transfection of miR-133b and miR-135a reduced viability and induced apoptosis by inhibition of JAK2 expression and its phosphorylation and activation of caspase 3 and 7 in all three ccRCC cell lines. p-STAT3 and Bcl-2 expression was reduced after miRNA transfection whereas only slight influence on Bcl-2 L11 (BIM) was detected. Our results demonstrate that miR-133b and miR-135a which are down-regulated in wildtype and mutated ccRCCs, induce apoptosis in vitro by a signaling cascade involving JAK2, STAT3 and Bcl-2. Therefore, over-expression of these miRNAs seems to functionally counteract oncogenic signalling pathways in ccRCCs.