| First Author | Xu H | Year | 2015 |
| Journal | Diabetologia | Volume | 58 |
| Issue | 10 | Pages | 2298-306 |
| PubMed ID | 26141787 | Mgi Jnum | J:226444 |
| Mgi Id | MGI:5697267 | Doi | 10.1007/s00125-015-3683-8 |
| Citation | Xu H, et al. (2015) The Ia-2beta intronic miRNA, miR-153, is a negative regulator of insulin and dopamine secretion through its effect on the Cacna1c gene in mice. Diabetologia 58(10):2298-306 |
| abstractText | AIMS/HYPOTHESIS: miR-153 is an intronic miRNA embedded in the genes that encode IA-2 (also known as PTPRN) and IA-2beta (also known as PTPRN2). Islet antigen (IA)-2 and IA-2beta are major autoantigens in type 1 diabetes and are important transmembrane proteins in dense core and synaptic vesicles. miR-153 and its host genes are co-regulated in pancreas and brain. The present experiments were initiated to decipher the regulatory network between miR-153 and its host gene Ia-2beta (also known as Ptprn2). METHODS: Insulin secretion was determined by ELISA. Identification of miRNA targets was assessed using luciferase assays and by quantitative real-time PCR and western blots in vitro and in vivo. Target protector was also employed to evaluate miRNA target function. RESULTS: Functional studies revealed that miR-153 mimic suppresses both glucose- and potassium-induced insulin secretion (GSIS and PSIS, respectively), whereas miR-153 inhibitor enhances both GSIS and PSIS. A similar effect on dopamine secretion also was observed. Using miRNA target prediction software, we found that miR-153 is predicted to target the 3'UTR region of the calcium channel gene, Cacna1c. Further studies confirmed that Cacna1c mRNA and protein are downregulated by miR-153 mimics and upregulated by miR-153 inhibitors in insulin-secreting freshly isolated mouse islets, in the insulin-secreting mouse cell line MIN6 and in the dopamine-secreting cell line PC12. CONCLUSIONS/INTERPRETATION: miR-153 is a negative regulator of both insulin and dopamine secretion through its effect on Cacna1c expression, which suggests that IA-2beta and miR-153 have opposite functional effects on the secretory pathway. |
