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

作者：Wang Lihua; Bu Pengcheng; Ai Yiwei; Srinivasan Tara; Chen Huanhuan Joyce; Xiang Kun; Lipkin Steven M^*; Shen Xiling^*

来源：eLife, 2016, 5: e14620.

DOI：10.7554/eLife.14620

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.

• 出版日期2016-4-14