dc.contributor.authorYan, TingDong
dc.contributor.authorOoi, Wen Fong
dc.contributor.authorQamra, Aditi
dc.contributor.authorCheung, Alice
dc.contributor.authorMa, DongLiang
dc.contributor.authorSundaram, Gopinath Meenakshi
dc.contributor.authorXu, Chang
dc.contributor.authorXing, Manjie
dc.contributor.authorPoon, LaiFong
dc.contributor.authorWang, Jing
dc.contributor.authorLoh, Yan Ping
dc.contributor.authorHo, Jess Hui Jie
dc.contributor.authorNg, Joscelyn Jun Quan
dc.contributor.authorMuhammad Khairul Ramlee
dc.contributor.authorAswad, Luay
dc.contributor.authorRozen, Steve G.
dc.contributor.authorGhosh, Sujoy
dc.contributor.authorBard, Frederic A.
dc.contributor.authorSampath, Prabha
dc.contributor.authorTergaonkar, Vinay
dc.contributor.authorDavies, James O.J.
dc.contributor.authorHughes, Jim R.
dc.contributor.authorGoh, Eyleen
dc.contributor.authorBi, Xuezhi
dc.contributor.authorFullwood, Melissa Jane
dc.contributor.authorTan, Patrick
dc.contributor.authorLi, Shang
dc.identifier.citationYan, T., Ooi, W. F., Qamra, A., Cheung, A., Ma, D., Sundaram, G. M., et al. (2018). HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis. Nature Communications, 9(1), 100-.en_US
dc.description.abstractThe 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.en_US
dc.description.sponsorshipNRF (Natl Research Foundation, S’pore)en_US
dc.description.sponsorshipMOE (Min. of Education, S’pore)en_US
dc.format.extent15 p.en_US
dc.relation.ispartofseriesNature Communicationsen_US
dc.rights© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_US
dc.titleHoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesisen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.versionPublished versionen_US

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