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let-7 Modulates Chromatin Configuration and Target Gene Repression through Regulation of the ARID3B Complex.
- Source :
-
Cell reports [Cell Rep] 2016 Jan 26; Vol. 14 (3), pp. 520-533. Date of Electronic Publication: 2016 Jan 14. - Publication Year :
- 2016
-
Abstract
- Let-7 is crucial for both stem cell differentiation and tumor suppression. Here, we demonstrate a chromatin-dependent mechanism of let-7 in regulating target gene expression in cancer cells. Let-7 directly represses the expression of AT-rich interacting domain 3B (ARID3B), ARID3A, and importin-9. In the absence of let-7, importin-9 facilitates the nuclear import of ARID3A, which then forms a complex with ARID3B. The nuclear ARID3B complex recruits histone demethylase 4C to reduce histone 3 lysine 9 trimethylation and promotes the transcription of stemness factors. Functionally, expression of ARID3B is critical for the tumor initiation in let-7-depleted cancer cells. An inverse association between let-7 and ARID3A/ARID3B and prognostic significance is demonstrated in head and neck cancer patients. These results highlight a chromatin-dependent mechanism where let-7 regulates cancer stemness through ARID3B.<br /> (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Base Sequence
Cell Line
Chromatin metabolism
DNA-Binding Proteins antagonists & inhibitors
DNA-Binding Proteins genetics
Female
Histones metabolism
Humans
Karyopherins chemistry
Karyopherins genetics
Karyopherins metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs antagonists & inhibitors
MicroRNAs genetics
Neoplasms metabolism
Neoplasms mortality
Neoplasms pathology
Octamer Transcription Factor-3 genetics
Oligonucleotides, Antisense metabolism
RNA Interference
Sequence Alignment
Transcription Factors genetics
Transcription Factors metabolism
Transcriptome
Transplantation, Heterologous
DNA-Binding Proteins metabolism
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 14
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 26776511
- Full Text :
- https://doi.org/10.1016/j.celrep.2015.12.064