Abstract HOTAIR is a long non-coding RNA (lncRNA) which interacts with the Polycomb Repressive Complex and suppresses its target genes. HOTAIR has also been demonstrated to promote malignancy. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition (EMT) process and the expression of miR-141 is inversely correlated with tumorigenicity and invasiveness in several human cancers. We found that HOTAIR expression is inversely correlated to miR-141 expression in renal carcinoma cells. HOTAIR promotes malignancy including proliferation and invasion whereas miR-141 suppresses malignancy in renal carcinoma cells. miR-141 binds to HOTAIR in a sequence specific manner, and suppresses HOTAIR expression and functions including proliferation and invasion. Both HOTAIR and miR-141 were associated with the immunoprecipitated Argaunaute2 (Ago2) complex and the Ago2 complex cleaved HOTAIR in the presence of miR-141. These results demonstrate that HOTAIR is suppressed by miR-141 in an Ago2 dependent manner. Citation Format: Takeshi Chiyomaru, Shinichiro Fukuhara1, Sharanjot Saini, Shahana Majid, Guoren Deng, Varahram Shahryary, Inik Chang, Yuichiro Tanaka, Hideki Enokida, Masayuki Nakagawa, Rajvir Dahiya, Soichiro Yamamura. Long noncoding RNA HOTAIR is targeted and regulated by microRNA-141 in renal carcinoma cells. [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 4357. doi:10.1158/1538-7445.AM2014-4357