A long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division.
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.
Type
Journal articleSubject
asymmetric divisioncancer biology
cancer stem cell
colon cancer
developmental biology
human
methylation
non-coding RNA
stem cells
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https://hdl.handle.net/10161/12053Published Version (Please cite this version)
10.7554/eLife.14620Publication Info
Wang, Lihua; Bu, Pengcheng; Ai, Yiwei; Srinivasan, Tara; Chen, Huanhuan Joyce; Xiang,
Kun; ... Shen, Xiling (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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
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 Biolog

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