TY - JOUR
T1 - HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis
AU - Yan, Tingdong
AU - Ooi, Wen Fong
AU - Qamra, Aditi
AU - Cheung, Alice
AU - Ma, Dongliang
AU - Sundaram, Gopinath Meenakshi
AU - Xu, Chang
AU - Xing, Manjie
AU - Poon, Laifong
AU - Wang, Jing
AU - Loh, Yan Ping
AU - Ho, Jess Hui Jie
AU - Ng, Joscelyn Jun Quan
AU - Ramlee, Muhammad Khairul
AU - Aswad, Luay
AU - Rozen, Steve G.
AU - Ghosh, Sujoy
AU - Bard, Frederic A.
AU - Sampath, Prabha
AU - Tergaonkar, Vinay
AU - Davies, James O.J.
AU - Hughes, Jim R.
AU - Goh, Eyleen
AU - Bi, Xuezhi
AU - Fullwood, Melissa Jane
AU - Tan, Patrick
AU - Li, Shang
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85042791044
U2 - 10.1038/s41467-017-02601-1
DO - 10.1038/s41467-017-02601-1
M3 - 文章
C2 - 29311615
AN - SCOPUS:85042791044
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 100
ER -
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