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Title: HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis
Authors: Bi, Xuezhi
Muhammad Khairul Ramlee
Davies, James O.J.
Yan, TingDong
Ooi, Wen Fong
Qamra, Aditi
Cheung, Alice
Ma, DongLiang
Sundaram, Gopinath Meenakshi
Xu, Chang
Xing, Manjie
Poon, LaiFong
Wang, Jing
Loh, Yan Ping
Ho, Jess Hui Jie
Ng, Joscelyn Jun Quan
Aswad, Luay
Rozen, Steve G.
Ghosh, Sujoy
Bard, Frederic A.
Sampath, Prabha
Tergaonkar, Vinay
Hughes, Jim R.
Goh, Eyleen
Fullwood, Melissa Jane
Tan, Patrick
Li, Shang
Keywords: Tumorigenesis
Issue Date: 2017
Source: Yan, 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-.
Series/Report no.: Nature Communications
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.
DOI: 10.1038/s41467-017-02601-1
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
Fulltext Permission: open
Fulltext Availability: With Fulltext
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