BRM transcriptionally regulates miR-302a-3p to target SOCS5/STAT3 signaling axis to potentiate pancreatic cancer metastasis.
Adult
Animals
Case-Control Studies
Cell Line, Tumor
Cell Movement
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Mice, Nude
MicroRNAs
/ genetics
Middle Aged
Neoplasm Metastasis
Pancreatic Neoplasms
/ genetics
Phosphorylation
STAT3 Transcription Factor
/ genetics
Signal Transduction
Suppressor of Cytokine Signaling Proteins
/ genetics
Transcription Factors
/ genetics
Transcription, Genetic
Xenograft Model Antitumor Assays
Young Adult
BRM
Metastasis
Pancreatic cancer
SOCS5
STAT3
miR-302a-3p
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
01 05 2019
01 05 2019
Historique:
received:
04
12
2018
revised:
03
02
2019
accepted:
14
02
2019
pubmed:
23
2
2019
medline:
6
2
2020
entrez:
22
2
2019
Statut:
ppublish
Résumé
Brahma (BRM) has recently been documented as a significant predictor of pancreatic cancer (PC) metastasis. This study aimed to further elucidate molecular mechanism by which BRM promotes PC metastasis. We found that silencing BRM reduced PC cell migration and invasion both in vivo and in vitro, accompanied by reduced level of miR-302a-3p. BRM positively regulated the transcription of miR-302a-3p, which acted as a metastasis-promoting miRNA in PC cells. miR-302a-3p directly targeted SOCS5 to boost STAT3 phosphorylation and induce the transcription of STAT3 target genes. Furthermore, miR-302a-3p level was higher in tissue and plasma samples derived from PC patients, and was significantly associated with worse clinical pathological features. In xenograft models, inhibiting miR-302a-3p was synergistically lethal in BRM-silenced PC cells. In conclusion, our results suggest that transcriptional regulation of miR-302a-3p by BRM potentiates PC metastasis by epigenetically suppressing SOCS5 expression and activating STAT3 signaling. These new findings provide potential therapeutic avenues for preventing PC-associated death.
Identifiants
pubmed: 30790683
pii: S0304-3835(19)30109-0
doi: 10.1016/j.canlet.2019.02.031
pii:
doi:
Substances chimiques
MIRN302A microRNA, human
0
MicroRNAs
0
SMARCA2 protein, human
0
SOCS5 protein, human
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Suppressor of Cytokine Signaling Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
215-225Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.