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

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2016-04-14

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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.

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10.7554/eLife.14620

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Wang, Lihua, Pengcheng Bu, Yiwei Ai, Tara Srinivasan, Huanhuan Joyce Chen, Kun Xiang, Steven M Lipkin, Xiling Shen, et al. (2016). A long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division. Elife, 5. 10.7554/eLife.14620 Retrieved from https://hdl.handle.net/10161/12053.

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Xiling Shen

Adjunct Professor in the Department of Pathology

Dr. Shen’s research interests lie at precision medicine and systems biology. His lab integrates engineering, computational and biological techniques to study cancer, stem cells, microbiota and the nervous system in the gut. This multidisciplinary work has been instrumental in initiating several translational clinical trials in precision therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP) and a core member of the Center for Genomics and Computational Biology (GCB).


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