miR-802 Suppresses Acinar-to-Ductal Reprogramming During Early Pancreatitis and Pancreatic Carcinogenesis.
Acinar Cells
/ metabolism
Animals
Carcinoma, Pancreatic Ductal
/ genetics
Cell Line, Tumor
Cell Proliferation
Cell Transformation, Neoplastic
/ genetics
Cellular Reprogramming
Disease Models, Animal
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Mice, Transgenic
MicroRNAs
/ genetics
Mutation
Pancreas
/ metabolism
Pancreatic Neoplasms
/ genetics
Pancreatitis
/ genetics
Proto-Oncogene Proteins p21(ras)
/ genetics
SOX9 Transcription Factor
/ genetics
Signal Transduction
Micro-RNA
Pancreatic Cancer
Pancreatitis
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
06
05
2021
revised:
25
08
2021
accepted:
14
09
2021
pubmed:
22
9
2021
medline:
19
1
2022
entrez:
21
9
2021
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor that is almost uniformly lethal in humans. Activating mutations of KRAS are found in >90% of human PDACs and are sufficient to promote acinar-to-ductal metaplasia (ADM) during tumor initiation. The roles of miRNAs in oncogenic Kras-induced ADM are incompletely understood. The Ptf1a We show that miR-802 is a highly abundant and acinar-enriched pancreatic miRNA that is silenced during early stages of injury or oncogenic Kras We show miR-802 suppresses pancreatic cancer initiation by repressing oncogenic Kras-induced ADM. The role of miR-802 in ADM fills the gap in our understanding of oncogenic Kras-induced F-actin reorganization, acinar reprogramming, and PDAC initiation. Modulation of the miR-802-RhoA-F-actin network may be a new strategy to interfere with pancreatic carcinogenesis.
Sections du résumé
BACKGROUND & AIMS
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor that is almost uniformly lethal in humans. Activating mutations of KRAS are found in >90% of human PDACs and are sufficient to promote acinar-to-ductal metaplasia (ADM) during tumor initiation. The roles of miRNAs in oncogenic Kras-induced ADM are incompletely understood.
METHODS
The Ptf1a
RESULTS
We show that miR-802 is a highly abundant and acinar-enriched pancreatic miRNA that is silenced during early stages of injury or oncogenic Kras
CONCLUSIONS
We show miR-802 suppresses pancreatic cancer initiation by repressing oncogenic Kras-induced ADM. The role of miR-802 in ADM fills the gap in our understanding of oncogenic Kras-induced F-actin reorganization, acinar reprogramming, and PDAC initiation. Modulation of the miR-802-RhoA-F-actin network may be a new strategy to interfere with pancreatic carcinogenesis.
Identifiants
pubmed: 34547282
pii: S0016-5085(21)03529-0
doi: 10.1053/j.gastro.2021.09.029
pii:
doi:
Substances chimiques
MIRN802 microRNA, human
0
MIRN802 microRNA, mouse
0
MicroRNAs
0
SOX9 Transcription Factor
0
SOX9 protein, human
0
Sox9 protein, mouse
0
Hras protein, mouse
EC 3.6.5.2
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
269-284Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.