MiR-132 controls pancreatic beta cell proliferation and survival through Pten/Akt/Foxo3 signaling.
Animals
Cell Proliferation
Cell Survival
Cells, Cultured
Forkhead Box Protein O3
/ metabolism
HEK293 Cells
Humans
Insulin-Secreting Cells
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs
/ genetics
PTEN Phosphohydrolase
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
Apoptosis
Pancreatectomy
Pten/Akt/Foxo3a
miR-132
β cell regeneration
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
20
06
2019
revised:
09
11
2019
accepted:
15
11
2019
entrez:
11
1
2020
pubmed:
11
1
2020
medline:
2
1
2021
Statut:
ppublish
Résumé
MicroRNAs (miRNAs) play an integral role in maintaining beta cell function and identity. Deciphering their targets and precise role, however, remains challenging. In this study, we aimed to identify miRNAs and their downstream targets involved in the regeneration of islet beta cells following partial pancreatectomy in mice. RNA from laser capture microdissected (LCM) islets of partially pancreatectomized and sham-operated mice were profiled with microarrays to identify putative miRNAs implicated in beta cell regeneration. Altered expression of the selected miRNAs, including miR-132, was verified by RT-PCR. Potential targets of miR-132 were selected through bioinformatic data mining. Predicted miR-132 targets were validated for their changed RNA, protein expression levels, and signaling upon miR-132 knockdown and/or overexpression in mouse MIN6 and human EndoC-βH1 insulinoma cells. The ability of miR-132 to foster beta cell proliferation in vivo was further assessed in pancreatectomized miR-132 Partial pancreatectomy significantly increased the number of BrdU This study provides compelling evidence about the critical role of miR-132 for the regeneration of mouse islet beta cells through the downregulation of its target Pten. Hence, the miR-132/Pten/Akt/Foxo3 signaling pathway may represent a suitable target to enhance beta cell mass.
Identifiants
pubmed: 31918917
pii: S2212-8778(19)30944-5
doi: 10.1016/j.molmet.2019.11.012
pmc: PMC6928290
pii:
doi:
Substances chimiques
Forkhead Box Protein O3
0
FoxO3 protein, mouse
0
MIRN132 microRNA, mouse
0
MicroRNAs
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
PTEN Phosphohydrolase
EC 3.1.3.67
Pten protein, mouse
EC 3.1.3.67
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
150-162Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier GmbH.. All rights reserved.
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