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J Cell Sci. 2021 Dec 15;134(24). doi: 10.1242/jcs.259306. Epub 2021 Dec 20.

The tumor-suppressive long noncoding RNA DRAIC inhibits protein translation and induces autophagy by activating AMPK.

Journal of cell science

Shekhar Saha, Ying Zhang, Briana Wilson, Roger Abounader, Anindya Dutta

Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22901, USA.
  2. Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22901, USA.
  3. Cancer Center, University of Virginia, Charlottesville, Virginia 22901, USA.
  4. Department of Genetics, University of Alabama, Birmingham, Alabama 35233, USA.

PMID: 34746949 PMCID: PMC8729785 DOI: 10.1242/jcs.259306

Abstract

Long noncoding RNAs (lncRNAs) are long RNA transcripts that do not code for proteins and have been shown to play a major role in cellular processes through diverse mechanisms. DRAIC, a lncRNA that is downregulated in castration-resistant advanced prostate cancer, inhibits the NF-κB pathway by inhibiting the IκBα 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 AMP-activated protein kinase (AMPK) by downregulating the NF-κB target gene GLUT1, and thus represses mTOR, leading to downstream effects, such as a decrease in protein translation and increase in autophagy. DRAIC, therefore, has an effect on multiple signal transduction pathways that are important for oncogenesis, namely, the NF-κB pathway and AMPK-mTOR-S6K/ULK1 pathway. The regulation of NF-κB, 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. This article has an associated First Person interview with the first author of the paper.

© 2021. Published by The Company of Biologists Ltd.

Keywords: AMPK; Autophagy; DRAIC lncRNA; Protein translation; mTORC1

Conflict of interest statement

Competing interests The authors declare no competing or financial interests.

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