A tumor suppressive long noncoding RNA, DRAIC, inhibits protein translation and induces autophagy by activating AMPK

Abstract

LncRNAs are long RNA transcripts that do not code for proteins and that have been shown to play a major role in cellular processes through diverse mechanisms. DRAIC, a lncRNA which is downregulated in castration-resistant advanced prostate cancer, inhibits the NF-kB pathway by inhibiting the I{kappa}B kinase. Decreased DRAIC expression predicted poor patient outcome in gliomas and seven other cancers. We now report that DRAIC suppresses invasion, migration, colony formation and xenograft growth of glioblastoma derived cell lines. DRAIC activates AMPK by downregulating the NF-{kappa}B target gene GLUT1, and thus represses mTOR, leading to downstream effects such as decrease in protein translation and increase in autophagy. DRAIC, therefore, has an effect on multiple signal transduction pathways that are important for oncogenesis: the NF-{kappa}B pathway and AMPK-mTOR-S6K/ULK1 pathway. The regulation of NF-{kappa}B, protein translation and autophagy by the same lncRNA explains the tumor suppressive role of DRAIC in different cancers and reinforces the importance of lncRNAs as emerging regulators of signal transduction pathways.