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

TingDong Yan, Wen Fong Ooi, Aditi Qamra, Alice Cheung, DongLiang Ma, Gopinath Meenakshi Sundaram, Chang Xu, Manjie Xing, LaiFong Poon, Jing Wang, Yan Ping Loh, Jess Hui Jie Ho, Joscelyn Jun Quan Ng, Muhammad Khairul Ramlee, Luay Aswad, Steve G. Rozen, Sujoy Ghosh, Frederic A. Bard, Prabha Sampath, Vinay Tergaonkar, James O. J. Davies, Jim R. Hughes, Eyleen Goh, Xuezhi Bi, Melissa Jane Fullwood, Patrick Tan and Shang Li ()
Additional contact information
TingDong Yan: Duke-NUS Medical School
Wen Fong Ooi: Genome Institute of Singapore
Aditi Qamra: Genome Institute of Singapore
Alice Cheung: Duke-NUS Medical School
DongLiang Ma: Duke-NUS Medical School
Gopinath Meenakshi Sundaram: Institute of Medical Biology (IMB)
Chang Xu: Duke-NUS Medical School
Manjie Xing: Duke-NUS Medical School
LaiFong Poon: Duke-NUS Medical School
Jing Wang: Duke-NUS Medical School
Yan Ping Loh: National University of Singapore
Jess Hui Jie Ho: Duke-NUS Medical School
Joscelyn Jun Quan Ng: Duke-NUS Medical School
Muhammad Khairul Ramlee: Duke-NUS Medical School
Luay Aswad: National University of Singapore
Steve G. Rozen: Duke-NUS Medical School
Sujoy Ghosh: Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
Frederic A. Bard: Institute of Molecular and Cell Biology (IMCB)
Prabha Sampath: Duke-NUS Medical School
Vinay Tergaonkar: Institute of Molecular and Cell Biology (IMCB)
James O. J. Davies: Oxford University
Jim R. Hughes: Oxford University
Eyleen Goh: National University of Singapore
Xuezhi Bi: Bioprocessing Technology Institute
Melissa Jane Fullwood: National University of Singapore
Patrick Tan: Duke-NUS Medical School
Shang Li: Duke-NUS Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02601-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02601-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02601-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().