Abstract
Abstract Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents the most common renal histology. To identify a novel biomarker or a candidate target of molecular-targeted drug for ccRCC, we focused on miRNA expression signatures obtained from ccRCC clinical specimens by miRNA-microarray. The expression signatures revealed that miR-629 was significantly up-regulated in ccRCC specimens compared to normal specimens. Inhibition of miR-629 through a hairpin miRNA inhibitor inhibited cell migration and invasion. We found that miR-629 directly targets the Tripartite motif-containing 33 (TRIM33) an inhibitor of TGF-β/Smad signaling pathway. Inhibition of miR-629 significantly suppressed TGF-β -induced Smad activation through up-regulation of TRIM33 expression and subsequent inhibition of Smad2/3 and Smad4 binding. Furthermore, miR-629 inhibition attenuated the effect of TGF-β on expression of EMT-related factors and cell migration and invasion. Finally, in human clinical specimens, TRIM33 was down-regulated where an association with pathological stage and grade. Our findings identify miR-629 as a potent regulator of TGF-β/Smad signaling pathway and functions as an oncomir, which may provide a novel therapeutic strategy for treatment of ccRCC. Citation Format: Kentaro Jingushi, Wataru Nakata, Yuko Ueda, Kaori Kitae, Kazutoshi Fujita, Motohide Uemura, Norio Nonomura, Kazutake Tsujikawa. MiR-629 targets TRIM33 to promote TGF-β/Smad signaling in clear cell renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5197. doi:10.1158/1538-7445.AM2014-5197
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call