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 | |
dc.contributor.author | Ai, Yiwei | |
dc.contributor.author | Srinivasan, Tara | |
dc.contributor.author | Chen, Huanhuan Joyce | |
dc.contributor.author | Xiang, Kun | |
dc.contributor.author | Lipkin, Steven M | |
dc.contributor.author | 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 | ||
dc.identifier.eissn | 2050-084X | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | eLife Sciences Publications, Ltd | |
dc.relation.ispartof | Elife | |
dc.relation.isversionof | 10.7554/eLife.14620 | |
dc.subject | asymmetric division | |
dc.subject | cancer biology | |
dc.subject | cancer stem cell | |
dc.subject | colon cancer | |
dc.subject | developmental biology | |
dc.subject | human | |
dc.subject | methylation | |
dc.subject | non-coding RNA | |
dc.subject | 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 | ||
pubs.organisational-group | Biomedical Engineering | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Pratt School of Engineering | |
pubs.organisational-group | School of Medicine | |
pubs.publication-status | Published online | |
pubs.volume | 5 |
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