| First Author | Mandemakers W | Year | 2013 |
| Journal | Diabetologia | Volume | 56 |
| Issue | 7 | Pages | 1547-56 |
| PubMed ID | 23595248 | Mgi Jnum | J:198964 |
| Mgi Id | MGI:5499953 | Doi | 10.1007/s00125-013-2901-5 |
| Citation | Mandemakers W, et al. (2013) Co-regulation of intragenic microRNA miR-153 and its host gene Ia-2 beta: identification of miR-153 target genes with functions related to IA-2beta in pancreas and brain. Diabetologia 56(7):1547-56 |
| abstractText | AIMS/HYPOTHESIS: We analysed the genomic organisation of miR-153, a microRNA embedded in genes that encode two of the major type 1 diabetes autoantigens, islet-associated protein (IA)-2 and IA-2beta. We also identified miR-153 target genes that correlated with IA-2beta localisation and function. METHODS: A bioinformatics approach was used to identify miR-153's genomic organisation. To analyse the co-regulation of miR-153 and IA-2beta, quantitative PCR analysis of miR-153 and Ia-2beta (also known as Ptprn2) was performed after a glucose stimulation assay in MIN6B cells and isolated murine pancreatic islets, and also in wild-type Ia-2 (also known as Ptprn), Ia-2beta single knockout and Ia-2/Ia-2beta double knockout mouse brain and pancreatic islets. Bioinformatics identification of miR-153 target genes and validation via luciferase reporter assays, western blotting and quantitative PCR were also carried out. RESULTS: Two copies of miR-153, miR-153-1 and miR-153-2, are localised in intron 19 of Ia-2 and Ia-2beta, respectively. In rodents, only miR-153-2 is conserved. We demonstrated that expression of miR-153-2 and Ia-2beta in rodents is partially co-regulated as demonstrated by a strong reduction of miR-153 expression levels in Ia-2beta knockout and Ia-2/Ia-2beta double knockout mice. miR-153 levels were unaffected in Ia-2 knockout mice. In addition, glucose stimulation, which increases Ia-2 and Ia-2beta expression, also significantly increased expression of miR-153. Several predicted targets of miR-153 were reduced after glucose stimulation in vitro, correlating with the increase in miR-153 levels. CONCLUSIONS/INTERPRETATION: This study suggests the involvement of miR-153, IA-2beta and miR-153 target genes in a regulatory network, which is potentially relevant to insulin and neurotransmitter release. |
