Transcriptional regulation of the miR-212/miR-132 cluster in insulin-secreting β-cells by cAMP-regulated transcriptional co-activator 1 and salt-inducible kinases.
Malm, Helena LU ; Mollet, Ines LU ; Berggreen, Christine LU ; Orho-Melander, Marju LU ; Esguerra, Jonathan LU
; Göransson, Olga
LU
and Eliasson, Lena
LU
(2016)
In Molecular and Cellular Endocrinology
424.
p.23-33
- Abstract
- MicroRNAs are central players in the control of insulin secretion, but their transcriptional regulation is poorly understood. Our aim was to investigate cAMP-mediated transcriptional regulation of the miR-212/miR-132 cluster and involvement of further upstream proteins in insulin secreting β-cells. cAMP induced by forskolin+IBMX or GLP-1 caused increased expression of miR-212/miR-132, and elevated phosphorylation of cAMP-response-element-binding-protein (CREB)/Activating-transcription-factor-1 (ATF1) and Salt-Inducible-Kinases (SIKs). CyclicAMP-Regulated Transcriptional Co-activator-1 (CRTC1) was concomitantly dephosphorylated and translocated to the nucleus. Silencing of miR-212/miR-132 reduced, and overexpression of miR-212 increased,... (More)
- MicroRNAs are central players in the control of insulin secretion, but their transcriptional regulation is poorly understood. Our aim was to investigate cAMP-mediated transcriptional regulation of the miR-212/miR-132 cluster and involvement of further upstream proteins in insulin secreting β-cells. cAMP induced by forskolin+IBMX or GLP-1 caused increased expression of miR-212/miR-132, and elevated phosphorylation of cAMP-response-element-binding-protein (CREB)/Activating-transcription-factor-1 (ATF1) and Salt-Inducible-Kinases (SIKs). CyclicAMP-Regulated Transcriptional Co-activator-1 (CRTC1) was concomitantly dephosphorylated and translocated to the nucleus. Silencing of miR-212/miR-132 reduced, and overexpression of miR-212 increased, glucose-stimulated insulin secretion. Silencing of CRTC1 expression resulted in decreased insulin secretion and miR-212/miR-132 expression, while silencing or inhibition of SIKs was associated with increased expression of the microRNAs and dephosphorylation of CRTC1. CRTC1 protein levels were reduced after silencing of miR-132, suggesting feed-back regulation. Our data propose cAMP-dependent co-regulation of miR-212/miR-132, in part mediated through SIK-regulated CRTC1, as an important factor for fine-tuned regulation of insulin secretion. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8576611
- author
- Malm, Helena
LU
; Mollet, Ines
LU
; Berggreen, Christine
LU
; Orho-Melander, Marju
LU
; Esguerra, Jonathan
LU
; Göransson, Olga
LU
and Eliasson, Lena
LU
- organization
- publishing date
- 2016-01-13
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular and Cellular Endocrinology
- volume
- 424
- pages
- 23 - 33
- publisher
- Elsevier
- external identifiers
-
- pmid:26797246
- scopus:84959238487
- wos:000372675200003
- pmid:26797246
- ISSN
- 1872-8057
- DOI
- 10.1016/j.mce.2016.01.010
- language
- English
- LU publication?
- yes
- id
- 56244b4b-8b84-4370-b4e2-d14bbba943b1 (old id 8576611)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26797246?dopt=Abstract
- date added to LUP
- 2016-04-04 08:55:45
- date last changed
- 2024-01-12 07:41:46
@article{56244b4b-8b84-4370-b4e2-d14bbba943b1,
abstract = {{MicroRNAs are central players in the control of insulin secretion, but their transcriptional regulation is poorly understood. Our aim was to investigate cAMP-mediated transcriptional regulation of the miR-212/miR-132 cluster and involvement of further upstream proteins in insulin secreting β-cells. cAMP induced by forskolin+IBMX or GLP-1 caused increased expression of miR-212/miR-132, and elevated phosphorylation of cAMP-response-element-binding-protein (CREB)/Activating-transcription-factor-1 (ATF1) and Salt-Inducible-Kinases (SIKs). CyclicAMP-Regulated Transcriptional Co-activator-1 (CRTC1) was concomitantly dephosphorylated and translocated to the nucleus. Silencing of miR-212/miR-132 reduced, and overexpression of miR-212 increased, glucose-stimulated insulin secretion. Silencing of CRTC1 expression resulted in decreased insulin secretion and miR-212/miR-132 expression, while silencing or inhibition of SIKs was associated with increased expression of the microRNAs and dephosphorylation of CRTC1. CRTC1 protein levels were reduced after silencing of miR-132, suggesting feed-back regulation. Our data propose cAMP-dependent co-regulation of miR-212/miR-132, in part mediated through SIK-regulated CRTC1, as an important factor for fine-tuned regulation of insulin secretion.}},
author = {{Malm, Helena and Mollet, Ines and Berggreen, Christine and Orho-Melander, Marju and Esguerra, Jonathan and Göransson, Olga and Eliasson, Lena}},
issn = {{1872-8057}},
language = {{eng}},
month = {{01}},
pages = {{23--33}},
publisher = {{Elsevier}},
series = {{Molecular and Cellular Endocrinology}},
title = {{Transcriptional regulation of the miR-212/miR-132 cluster in insulin-secreting β-cells by cAMP-regulated transcriptional co-activator 1 and salt-inducible kinases.}},
url = {{http://dx.doi.org/10.1016/j.mce.2016.01.010}},
doi = {{10.1016/j.mce.2016.01.010}},
volume = {{424}},
year = {{2016}},
}