Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-017-02601-1
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dc.titleHoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis
dc.contributor.authorYan, T
dc.contributor.authorOoi, W.F
dc.contributor.authorQamra, A
dc.contributor.authorCheung, A
dc.contributor.authorMa, D
dc.contributor.authorSundaram, G.M
dc.contributor.authorXu, C
dc.contributor.authorXing, M
dc.contributor.authorPoon, L
dc.contributor.authorWang, J
dc.contributor.authorLoh, Y.P
dc.contributor.authorHo, J.H.J
dc.contributor.authorNg, J.J.Q
dc.contributor.authorRamlee, M.K
dc.contributor.authorAswad, L
dc.contributor.authorRozen, S.G
dc.contributor.authorGhosh, S
dc.contributor.authorBard, F.A
dc.contributor.authorSampath, P
dc.contributor.authorTergaonkar, V
dc.contributor.authorDavies, J.O.J
dc.contributor.authorHughes, J.R
dc.contributor.authorGoh, E
dc.contributor.authorBi, X
dc.contributor.authorFullwood, M.J
dc.contributor.authorTan, P
dc.contributor.authorLi, S
dc.date.accessioned2020-09-04T02:17:44Z
dc.date.available2020-09-04T02:17:44Z
dc.date.issued2018
dc.identifier.citationYan, 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
dc.identifier.issn2041-1723
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174312
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. © 2017 The Author(s).
dc.publisherNature Publishing Group
dc.sourceUnpaywall 20200831
dc.subjectmicroRNA
dc.subjectmicroRNA 615 3p
dc.subjectunclassified drug
dc.subjecthomeodomain protein
dc.subjectHOXC5 protein, human
dc.subjectmicroRNA
dc.subjectMIRN615 microRNA, human
dc.subjecttelomerase
dc.subjectTERT protein, human
dc.subjectaging
dc.subjectcancer
dc.subjectcell
dc.subjectdifferentiation
dc.subjectembryonic development
dc.subjectgene expression
dc.subjectgenome
dc.subjectinhibition
dc.subjectphysiology
dc.subjectprimate
dc.subjecttumor
dc.subject3' untranslated region
dc.subject5' untranslated region
dc.subjectArticle
dc.subjectcarcinogenesis
dc.subjectcell differentiation
dc.subjectenhancer region
dc.subjectgene
dc.subjecthoxc5 gene
dc.subjecthuman
dc.subjecthuman cell
dc.subjectintron
dc.subjectreverse transcription polymerase chain reaction
dc.subjectanimal
dc.subjectbiosynthesis
dc.subjectcell transformation
dc.subjectgenetics
dc.subjectHEK293 cell line
dc.subjectHeLa cell line
dc.subjectHep-G2 cell line
dc.subjectMCF-7 cell line
dc.subjectmouse
dc.subjectneoplasm
dc.subjectpathology
dc.subjectpromoter region
dc.subjecttumor cell line
dc.subjectMammalia
dc.subjectPrimates
dc.subject3' Untranslated Regions
dc.subject5' Untranslated Regions
dc.subjectAnimals
dc.subjectCell Differentiation
dc.subjectCell Line, Tumor
dc.subjectCell Transformation, Neoplastic
dc.subjectEnhancer Elements, Genetic
dc.subjectHEK293 Cells
dc.subjectHeLa Cells
dc.subjectHep G2 Cells
dc.subjectHomeodomain Proteins
dc.subjectHumans
dc.subjectMCF-7 Cells
dc.subjectMice
dc.subjectMicroRNAs
dc.subjectNeoplasms
dc.subjectPromoter Regions, Genetic
dc.subjectTelomerase
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.description.doi10.1038/s41467-017-02601-1
dc.description.sourcetitleNature Communications
dc.description.volume9
dc.description.issue1
dc.description.page100
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