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https://doi.org/10.1038/s41467-017-02601-1
| Title: | HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis | Authors: | Yan, T Ooi, W.F Qamra, A Cheung, A Ma, D Sundaram, G.M Xu, C Xing, M Poon, L Wang, J Loh, Y.P Ho, J.H.J Ng, J.J.Q Ramlee, M.K Aswad, L Rozen, S.G Ghosh, S Bard, F.A Sampath, P Tergaonkar, V Davies, J.O.J Hughes, J.R Goh, E Bi, X Fullwood, M.J Tan, P Li, S |
Keywords: | microRNA microRNA 615 3p unclassified drug homeodomain protein HOXC5 protein, human microRNA MIRN615 microRNA, human telomerase TERT protein, human aging cancer cell differentiation embryonic development gene expression genome inhibition physiology primate tumor 3' untranslated region 5' untranslated region Article carcinogenesis cell differentiation enhancer region gene hoxc5 gene human human cell intron reverse transcription polymerase chain reaction animal biosynthesis cell transformation genetics HEK293 cell line HeLa cell line Hep-G2 cell line MCF-7 cell line mouse neoplasm pathology promoter region tumor cell line Mammalia Primates 3' Untranslated Regions 5' Untranslated Regions Animals Cell Differentiation Cell Line, Tumor Cell Transformation, Neoplastic Enhancer Elements, Genetic HEK293 Cells HeLa Cells Hep G2 Cells Homeodomain Proteins Humans MCF-7 Cells Mice MicroRNAs Neoplasms Promoter Regions, Genetic Telomerase |
Issue Date: | 2018 | Publisher: | Nature Publishing Group | Citation: | Yan, T, Ooi, W.F, Qamra, A, Cheung, A, Ma, D, Sundaram, G.M, Xu, C, Xing, M, Poon, L, Wang, J, Loh, Y.P, Ho, J.H.J, Ng, J.J.Q, Ramlee, M.K, Aswad, L, Rozen, S.G, Ghosh, S, Bard, F.A, Sampath, P, Tergaonkar, V, Davies, J.O.J, Hughes, J.R, Goh, E, Bi, X, Fullwood, M.J, Tan, P, Li, S (2018). HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis. Nature Communications 9 (1) : 100. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-017-02601-1 | 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. © 2017 The Author(s). | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/174312 | ISSN: | 2041-1723 | DOI: | 10.1038/s41467-017-02601-1 |
| Appears in Collections: | Elements Staff Publications |
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