Abstract B19: Short chain fatty acids suppress mTOR activation in colon cancer cells via the long noncoding RNA rhabdomyosarcoma 2 associated transcript

Short chain fatty acids (SCFAs), derived from dietary fiber bacterial fermentation in the colon, exert multiple effects on colonic functions including tumor suppressing activities. Our previous studies found that SCFAs can induce autophagy in colon cancer cells via suppressing mTOR activities, but the mechanism involved is not well understood. Herein we identify rhabdomyosarcoma 2 associated transcript (RMST), a long non-coding RNA, and protein tyrosine phosphatase non-receptor type 7(PTPN7) as key mediators for SCFAs to suppress mTOR signaling. SCFAs induce the expression of RMST in colon cancer cells. RMST by itself is sufficient to suppress mTOR signaling and sensitize colon cancer cells to SCFAs induction of autophagy. Through profiling, PTPN7 was identified as an effector for both RMST and SCFAs to suppress mTOR signaling. RMST increases the expression of PTPN7 by recruiting RNAPII to its promoter region. The data delineate a novel RMST-PTPN7 cellular pathway, enlisted by SCFAs, to modulate mTOR activities. Citation Format: Jiuhui Wang, Daotai Nie. Short chain fatty acids suppress mTOR activation in colon cancer cells via the long noncoding RNA rhabdomyosarcoma 2 associated transcript. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr B19.