The IA-2/IA-2β Intronic miRNA, miR-153, is Implicated in Insulin Secretion

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NIDCR	MOLBIO-23

Authors

• H Xu
• L Abuhatzira
• C Gilberto
• A.L Notkins

Abstract

Mir-153 is an intronic miRNA embedded in the genes that encode IA-2 and IA-2β. The IA-2 and IA-2ß proteins are major autoantigens in type 1 diabetes and are important dense core vesicle transmembrane proteins. Previous studies from our laboratory showed that mir-153, its host genes and targets are all involved in a common regulatory network affecting hormone secretion. In the current experiments we show that miR-153 is highly expressed in mouse brain and pancreatic islets. Functional studies revealed that miR-153 mimics suppress both glucose and potassium-induced insulin secretion, whereas miR-153 inhibitors enhance both glucose and potassium-induced insulin secretion. Using miRNA target prediction software, we found that miR-153 binds to the 3’UTR region of the calcium channel gene, Cacna1c. Further studies confirmed that Cacna1c mRNA and protein are down- regulated by miR-153 mimics and up-regulated by miR-153 inhibitors in the mouse insulin secreting cell line MIN6 and in mouse primary pancreatic islets. From these and other studies we conclude that miR-153 is a negative regulator of insulin exocytosis, in part, through its effect on Cacna1c gene expression.

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