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HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis.

Publication ,  Journal Article
Yan, T; Ooi, WF; Qamra, A; Cheung, A; Ma, D; Sundaram, GM; Xu, C; Xing, M; Poon, L; Wang, J; Loh, YP; Ho, JHJ; Ng, JJQ; Ramlee, MK; Goh, E ...
Published in: Nat Commun
January 8, 2018

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 8, 2018

Volume

9

Issue

1

Start / End Page

100

Location

England

Related Subject Headings

  • Telomerase
  • Promoter Regions, Genetic
  • Neoplasms
  • MicroRNAs
  • Mice
  • MCF-7 Cells
  • Humans
  • Homeodomain Proteins
  • Hep G2 Cells
  • Hela Cells
 

Citation

APA
Chicago
ICMJE
MLA
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Yan, T., Ooi, W. F., Qamra, A., Cheung, A., Ma, D., Sundaram, G. M., … Li, S. (2018). HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis. Nat Commun, 9(1), 100. https://doi.org/10.1038/s41467-017-02601-1
Yan, TingDong, Wen Fong Ooi, Aditi Qamra, Alice Cheung, DongLiang Ma, Gopinath Meenakshi Sundaram, Chang Xu, et al. “HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis.Nat Commun 9, no. 1 (January 8, 2018): 100. https://doi.org/10.1038/s41467-017-02601-1.
Yan T, Ooi WF, Qamra A, Cheung A, Ma D, Sundaram GM, et al. HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis. Nat Commun. 2018 Jan 8;9(1):100.
Yan, TingDong, et al. “HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis.Nat Commun, vol. 9, no. 1, Jan. 2018, p. 100. Pubmed, doi:10.1038/s41467-017-02601-1.
Yan T, Ooi WF, Qamra A, Cheung A, Ma D, Sundaram GM, Xu C, Xing M, Poon L, Wang J, Loh YP, Ho JHJ, Ng JJQ, Ramlee MK, Aswad L, Rozen SG, Ghosh S, Bard FA, Sampath P, Tergaonkar V, Davies JOJ, Hughes JR, Goh E, Bi X, Fullwood MJ, Tan P, Li S. HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis. Nat Commun. 2018 Jan 8;9(1):100.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 8, 2018

Volume

9

Issue

1

Start / End Page

100

Location

England

Related Subject Headings

  • Telomerase
  • Promoter Regions, Genetic
  • Neoplasms
  • MicroRNAs
  • Mice
  • MCF-7 Cells
  • Humans
  • Homeodomain Proteins
  • Hep G2 Cells
  • Hela Cells