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

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

doi:10.7554/eLife.14620

eLife (Apr 2016)

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

Lihua Wang,
Pengcheng Bu,
Yiwei Ai,
Tara Srinivasan,
Huanhuan Joyce Chen,
Kun Xiang,
Steven M Lipkin,
Xiling Shen

Affiliations

Lihua Wang: Department of Biological and Environmental Engineering, Cornell University, Ithaca, United States
Pengcheng Bu: School of Electrical and Computer Engineering, Cornell University, Ithaca, United States; Department of Biomedical Engineering, Cornell University, Ithaca, United States; Department of Biomedical Engineering, Duke University, Durham, United States
Yiwei Ai: School of Electrical and Computer Engineering, Cornell University, Ithaca, United States; Department of Biomedical Engineering, Cornell University, Ithaca, United States
Tara Srinivasan: Department of Biomedical Engineering, Cornell University, Ithaca, United States
Huanhuan Joyce Chen: Meyer Cancer Center, Weill Corenll Medical College, New York, United States
Kun Xiang: Department of Biomedical Engineering, Cornell University, Ithaca, United States
Steven M Lipkin: Deparments of Medicine, Genetic Medicine and Surgery, Weill Cornell Medical College, New York, United States
Xiling Shen: ORCiD; Department of Biological and Environmental Engineering, Cornell University, Ithaca, United States; School of Electrical and Computer Engineering, Cornell University, Ithaca, United States; Department of Biomedical Engineering, Cornell University, Ithaca, United States; Department of Biomedical Engineering, Duke University, Durham, United States

DOI: https://doi.org/10.7554/eLife.14620
Journal volume & issue: Vol. 5

Abstract

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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.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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