Long non-coding RNA MANCR is a target of BET bromodomain protein BRD4 and plays a critical role in cellular migration and invasion abilities of prostate cancer.
Azepines
/ pharmacology
Cell Cycle Proteins
/ metabolism
Cell Line, Tumor
Cell Movement
/ drug effects
Down-Regulation
/ drug effects
Enhancer Elements, Genetic
/ genetics
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Male
Neoplasm Invasiveness
Prostatic Neoplasms
/ genetics
RNA, Untranslated
/ genetics
Transcription Factors
/ metabolism
Triazoles
/ pharmacology
BET protein inhibitor
Epithelial-mesenchymal transition
MANCR
Prostate cancer
Super-enhancer
lncRNA
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
21 05 2020
21 05 2020
Historique:
received:
22
02
2020
accepted:
09
03
2020
pubmed:
23
3
2020
medline:
25
11
2020
entrez:
23
3
2020
Statut:
ppublish
Résumé
Androgen receptor (AR)-negative castration-resistant prostate cancer (CRPC) is highly aggressive and is resistant to most of the current therapies. Bromodomain and extra terminal domain (BET) protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. A BET inhibitor, JQ1, has been found to suppress the malignant phenotypes of prostate cancer cells, however, the target genes of JQ1 remain largely unknown. Here we show that SE-associated genes specific for AR-negative CRPC PC3 cells include genes involved in migration and invasion, and that JQ1 impairs migration and invasion of PC3 cells. We identified a long non-coding RNA, MANCR, which was markedly down-regulated by JQ1, and found that BRD4 binds to the MANCR locus. MANCR knockdown led to a significant decrease in migration and invasion of PC3 cells. Furthermore, RNA sequencing analysis revealed that expression of the genes involved in migration and invasion was altered by MANCR knockdown. In summary, our data demonstrate that MANCR plays a critical role in migration and invasion of PC3 cells.
Identifiants
pubmed: 32199616
pii: S0006-291X(20)30522-2
doi: 10.1016/j.bbrc.2020.03.043
pii:
doi:
Substances chimiques
(+)-JQ1 compound
0
Azepines
0
BRD4 protein, human
0
Cell Cycle Proteins
0
RNA, Untranslated
0
Transcription Factors
0
Triazoles
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
128-134Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.