Identification of glucose-regulated miRNAs from pancreatic {beta} cells reveals a role for miR-30d in insulin transcription.
MicroRNAs (miRNAs) are small noncoding ribonucleotides that bind mRNAs and function mainly as translational repressors in mammals. MicroRNAs have been implicated to play a role in many diseases, including diabetes. Several reports indicate an important function for miRNAs in insulin production as well as insulin secretion. We have recently carried out a screen in the pancreatic beta-cell line MIN6 to identify miRNAs with altered abundance in response to changes in glucose concentrations. This screen resulted in identification of 61 glucose-regulated miRNAs from a total of 108 miRNAs detectable in MIN6 cells. Many of the identified miRNAs, including miR-124a, miR-107, and miR-30d were up-regulated in the presence of high glucose. Only a few of the miRNAs, including miR-296, miR-484, and miR-690 were significantly down-regulated by high glucose treatment. Interestingly, we found that overexpression of miR-30d, one of the miRNAs up-regulated by glucose, increased insulin gene expression, while inhibition of miR-30d abolished glucose-stimulated insulin gene transcription. Overexpression or inhibition of miR-30d did not have any effect on insulin secretion. These data suggest that the putative target genes of miR-30d may be negative regulators of insulin gene expression.
Tang
Xiaoqing
X
Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, Lexington, 40536, USA.
Muniappan
Latha
L
Tang
Guiliang
G
Ozcan
Sabire
S
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000378:metabolism; D007328:Insulin / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D005947:Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D035683:MicroRNAs; D015534:Trans-Activators; C534715:Mirn30d microRNA, mouse; C501008:Neurod1 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein