Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-017-02601-1
Title: HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis
Authors: Yan, T 
Ooi, W.F
Qamra, A 
Cheung, A 
Ma, D 
Sundaram, G.M
Xu, C 
Xing, M
Poon, L 
Wang, J 
Loh, Y.P 
Ho, J.H.J
Ng, J.J.Q
Ramlee, M.K
Aswad, L 
Rozen, S.G 
Ghosh, S 
Bard, F.A 
Sampath, P 
Tergaonkar, V 
Davies, J.O.J
Hughes, J.R
Goh, E 
Bi, X
Fullwood, M.J 
Tan, P 
Li, S 
Keywords: microRNA
microRNA 615 3p
unclassified drug
homeodomain protein
HOXC5 protein, human
microRNA
MIRN615 microRNA, human
telomerase
TERT protein, human
aging
cancer
cell
differentiation
embryonic development
gene expression
genome
inhibition
physiology
primate
tumor
3' untranslated region
5' untranslated region
Article
carcinogenesis
cell differentiation
enhancer region
gene
hoxc5 gene
human
human cell
intron
reverse transcription polymerase chain reaction
animal
biosynthesis
cell transformation
genetics
HEK293 cell line
HeLa cell line
Hep-G2 cell line
MCF-7 cell line
mouse
neoplasm
pathology
promoter region
tumor cell line
Mammalia
Primates
3' Untranslated Regions
5' Untranslated Regions
Animals
Cell Differentiation
Cell Line, Tumor
Cell Transformation, Neoplastic
Enhancer Elements, Genetic
HEK293 Cells
HeLa Cells
Hep G2 Cells
Homeodomain Proteins
Humans
MCF-7 Cells
Mice
MicroRNAs
Neoplasms
Promoter Regions, Genetic
Telomerase
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Yan, T, Ooi, W.F, Qamra, A, Cheung, A, Ma, D, Sundaram, G.M, Xu, C, Xing, M, Poon, L, Wang, J, Loh, Y.P, Ho, J.H.J, Ng, J.J.Q, Ramlee, M.K, Aswad, L, Rozen, S.G, Ghosh, S, Bard, F.A, Sampath, P, Tergaonkar, V, Davies, J.O.J, Hughes, J.R, Goh, E, Bi, X, Fullwood, M.J, Tan, P, Li, S (2018). HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis. Nature Communications 9 (1) : 100. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-017-02601-1
Abstract: The repression of telomerase activity during cellular differentiation promotes replicative aging and functions as a physiological barrier for tumorigenesis in long-lived mammals, including humans. However, the underlying mechanisms remain largely unclear. Here we describe how miR-615-3p represses hTERT expression. mir-615-3p is located in an intron of the HOXC5 gene, a member of the highly conserved homeobox family of transcription factors controlling embryogenesis and development. Unexpectedly, we found that HoxC5 also represses hTERT expression by disrupting the long-range interaction between hTERT promoter and its distal enhancer. The 3?UTR of hTERT and its upstream enhancer region are well conserved in long-lived primates. Both mir-615-3p and HOXC5 are activated upon differentiation, which constitute a feed-forward loop that coordinates transcriptional and post-Transcriptional repression of hTERT during cellular differentiation. Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers. © 2017 The Author(s).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/174312
ISSN: 2041-1723
DOI: 10.1038/s41467-017-02601-1
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