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

Molecular and Cellular Endocrinology
Helena Anna MalmLena Eliasson

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 fo...Continue Reading

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Citations

Oct 26, 2016·Frontiers in Endocrinology·Leonid E FridlyandLouis H Philipson
Jan 26, 2017·The International Journal of Biochemistry & Cell Biology·Louise Torp Dalgaard, Lena Eliasson
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May 28, 2017·Naunyn-Schmiedeberg's Archives of Pharmacology·Svenja BörchersElke Oetjen
Apr 22, 2020·Diabetes·Lena Eliasson, Jonathan L S Esguerra
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Jan 24, 2019·Nucleic Acid Therapeutics·Roel BijkerkAnton Jan van Zonneveld
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Jan 23, 2017·Diabetology International·Lena EliassonAnna Wendt
Jun 4, 2019·EBioMedicine·Kerstin RohdeYvonne Böttcher
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Oct 1, 2021·Endocrine Journal·Chunhu WangJiguang Ma

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