A long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division.

TitleA long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division.
Publication TypeJournal Article
Year of Publication2016
AuthorsWang, L, Bu, P, Ai, Y, Srinivasan, T, Chen, HJ, Xiang, K, Lipkin, SM, and Shen, X
JournaleLife
Volume5
Date Published04/2016
Abstract

The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initiates asymmetric division by directly targeting the microRNA miR-34a to cause its spatial imbalance. Lnc34a recruits Dnmt3a via PHB2 and HDAC1 to methylate and deacetylate the miR-34a promoter simultaneously, hence epigenetically silencing miR-34a expression independent of its upstream regulator, p53. Lnc34a levels affect CCSC self-renewal and colorectal cancer (CRC) growth in xenograft models. Lnc34a is upregulated in late-stage CRCs, contributing to epigenetic miR-34a silencing and CRC proliferation. The fact that lncRNA targets microRNA highlights the regulatory complexity of non-coding RNAs (ncRNAs), which occupy the bulk of the genome.

DOI10.7554/elife.14620
Short TitleeLife