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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

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, Shang Li

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. More... »

PAGES

100

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-017-02601-1

DOI

http://dx.doi.org/10.1038/s41467-017-02601-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100172276

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29311615


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