Back to Search
Start Over
HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis.
- Source :
-
Nature communications [Nat Commun] 2018 Jan 08; Vol. 9 (1), pp. 100. Date of Electronic Publication: 2018 Jan 08. - Publication Year :
- 2018
-
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.
- Subjects :
- 3' Untranslated Regions genetics
5' Untranslated Regions genetics
Animals
Cell Line, Tumor
Enhancer Elements, Genetic genetics
HEK293 Cells
HeLa Cells
Hep G2 Cells
Humans
MCF-7 Cells
Mice
Neoplasms genetics
Neoplasms pathology
Promoter Regions, Genetic genetics
Cell Differentiation genetics
Cell Transformation, Neoplastic genetics
Homeodomain Proteins genetics
MicroRNAs genetics
Telomerase biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 29311615
- Full Text :
- https://doi.org/10.1038/s41467-017-02601-1