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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)
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organization
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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
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
2016-02-03 21:59:57
date last changed
2017-09-24 04:40:10
@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},
  volume       = {424},
  year         = {2016},
}