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

dc.contributor.author

Wang, Lihua

dc.contributor.author

Bu, Pengcheng

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Ai, Yiwei

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Srinivasan, Tara

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Chen, Huanhuan Joyce

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Xiang, Kun

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Lipkin, Steven M

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Shen, Xiling

dc.coverage.spatial

England

dc.date.accessioned

2016-05-25T19:44:46Z

dc.date.issued

2016-04-14

dc.description.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.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/27077950

dc.identifier.eissn

2050-084X

dc.identifier.uri

https://hdl.handle.net/10161/12053

dc.language

eng

dc.publisher

eLife Sciences Publications, Ltd

dc.relation.ispartof

Elife

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10.7554/eLife.14620

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asymmetric division

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cancer biology

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cancer stem cell

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colon cancer

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developmental biology

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human

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methylation

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non-coding RNA

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stem cells

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Shen, Xiling|0000-0002-4978-3531

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/27077950

pubs.organisational-group

Biomedical Engineering

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Duke

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Duke Cancer Institute

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Institutes and Centers

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Pratt School of Engineering

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School of Medicine

pubs.publication-status

Published online

pubs.volume

5

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