Regulation of mTOR Signaling by Rhabdomyosarcoma 2-Associated Transcript (RMST): Role in Tumor Growth and Progression

The mammalian target of rapamycin (mTOR) signaling pathway is often aberrantly activated in cancers, including colorectal cancers. Long non-coding RNA (lncRNA) is a subset of non-coding transcripts with a minimum length of 200 nucleotides that can regulate multiple biological processes related to development, differentiation, metabolism, and carcinogenesis. By screening the lncRNAs required for short-chain fatty acids to suppress mTOR signaling, we have identified rhabdomyosarcoma 2-associated transcript (lncRNA RMST) as a novel regulator of mTOR and autophagy in colorectal cancer cells. Among its various transcript variants, linear RMST from exon 1 to exon 9 is sufficient to suppress mTOR signaling. Herein, we discuss the regulation of RMST gene expression, its expression patterns in cancers, and its clinical relevance. We also discuss the mechanism for RMST to suppress mTOR signaling and its possible abrogation during tumor growth and progression.