MicroRNA-365a-3p inhibits c-Rel-mediated NF-κB signaling and the progression of pancreatic cancer.
Animals
Anticarcinogenic Agents
/ pharmacology
Apoptosis
/ drug effects
Carcinoma, Pancreatic Ductal
/ genetics
Cell Line, Tumor
Cell Movement
/ drug effects
Chick Embryo
Disease Progression
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Isothiocyanates
/ pharmacology
MicroRNAs
/ drug effects
Pancreatic Neoplasms
/ genetics
Proto-Oncogene Proteins c-rel
/ metabolism
Signal Transduction
Sulfoxides
Transcription Factor RelA
/ metabolism
Xenograft Model Antitumor Assays
NF-κB signaling
Pancreatic cancer
Sulforaphane
microRNA
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
28 06 2019
28 06 2019
Historique:
received:
16
11
2018
revised:
19
03
2019
accepted:
19
03
2019
pubmed:
27
3
2019
medline:
27
2
2020
entrez:
27
3
2019
Statut:
ppublish
Résumé
NF-κB contributes to the aggressiveness of pancreatic ductal adenocarcinoma (PDA), which is counteracted by the bioactive agent sulforaphane. We investigated sulforaphane-induced microRNA signaling and its influence on progression features. Using established cell lines, microRNA and gene arrays, we predicted miR-365a as the top candidate for the sulforaphane-induced inhibition of the NF-κB subunit c-Rel. The lipofection of miR-365a-3p mimics inhibited the luciferase activity of a c-Rel 3'-UTR construct, as well as c-Rel expression, NF-κB activity, and tumor viability, migration, and clonogenicity, whereas apoptosis was induced. In vivo, miR-365a-3p reduced the volume of tumor xenografts and the expression of progression markers. In a tissue array, the expression of miR-365a-3p was absent in almost all 91 malignant tissues but not in 5 normal tissues, thus confirming the previous results. Our observations suggest that sulforaphane-induced miR-365a-3p expression inhibits NF-κB activity by downregulating c-Rel, which prevents the progression of PDA.
Identifiants
pubmed: 30910589
pii: S0304-3835(19)30181-8
doi: 10.1016/j.canlet.2019.03.025
pii:
doi:
Substances chimiques
Anticarcinogenic Agents
0
Isothiocyanates
0
MIRN365 microRNA, human
0
MicroRNAs
0
Proto-Oncogene Proteins c-rel
0
REL protein, human
0
RELA protein, human
0
Sulfoxides
0
Transcription Factor RelA
0
sulforaphane
GA49J4310U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
203-212Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.