MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes
<p style="text-align:justify;"> <b>Background:</b> MicroRNAs (miRNAs) are non-coding RNA molecules involved in post-transcriptional control of gene expression of a wide number of genes, including those involved in glucose homeostasis. Type 2 diabetes (T2D) is characteriz...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
BioMed Central
2009
|
| _version_ | 1797076034304081920 |
|---|---|
| author | Herrera, B Lockstone, H Taylor, J Wills, Q Kaisaki, P Barrett, A Camps, C Fernandez, C Ragoussis, J Gauguier, D McCarthy, M Lindgren, C |
| author_facet | Herrera, B Lockstone, H Taylor, J Wills, Q Kaisaki, P Barrett, A Camps, C Fernandez, C Ragoussis, J Gauguier, D McCarthy, M Lindgren, C |
| author_sort | Herrera, B |
| collection | OXFORD |
| description | <p style="text-align:justify;"> <b>Background:</b> MicroRNAs (miRNAs) are non-coding RNA molecules involved in post-transcriptional control of gene expression of a wide number of genes, including those involved in glucose homeostasis. Type 2 diabetes (T2D) is characterized by hyperglycaemia and defects in insulin secretion and action at target tissues. We sought to establish differences in global miRNA expression in two insulin-target tissues from inbred rats of spontaneously diabetic and normoglycaemic strains.<br/><br/> <b>Methods</b> We used a miRNA microarray platform to measure global miRNA expression in two insulin-target tissues: liver and adipose tissue from inbred rats of spontaneously diabetic (Goto-Kakizaki [GK]) and normoglycaemic (Brown-Norway [BN]) strains which are extensively used in genetic studies of T2D. MiRNA data were integrated with gene expression data from the same rats to investigate how differentially expressed miRNAs affect the expression of predicted target gene transcripts.<br/><br/> <b>Results:</b> The expression of 170 miRNAs was measured in liver and adipose tissue of GK and BN rats. Based on a p-value for differential expression between GK and BN, the most significant change in expression was observed for miR-125a in liver (FC = 5.61, P = 0.001, P adjusted = 0.10); this overexpression was validated using quantitative RT-PCR (FC = 13.15, P = 0.0005). MiR-125a also showed over-expression in the GK vs. BN analysis within adipose tissue (FC = 1.97, P = 0.078, P adjusted = 0.99), as did the previously reported miR-29a (FC = 1.51, P = 0.05, P adjusted = 0.99). In-silico tools assessing the biological role of predicted miR-125a target genes suggest an over-representation of genes involved in the MAPK signaling pathway. Gene expression analysis identified 1308 genes with significantly different expression between GK and BN rats (P adjusted < 0.05): 233 in liver and 1075 in adipose tissue. Pathways related to glucose and lipid metabolism were significantly over-represented among these genes. Enrichment analysis suggested that differentially expressed genes in GK compared to BN included more predicted miR-125a target genes than would be expected by chance in adipose tissue (FDR = 0.006 for up-regulated genes; FDR = 0.036 for down-regulated genes) but not in liver (FDR = 0.074 for up-regulated genes; FDR = 0.248 for down-regulated genes).<br/><br/> <b>Conclusion:</b> MiR-125a is over-expressed in liver in hyperglycaemic GK rats relative to normoglycaemic BN rats, and our array data also suggest miR-125a is over-expressed in adipose tissue. We demonstrate the use of in-silico tools to provide the basis for further investigation of the potential role of miR-125a in T2D. In particular, the enrichment of predicted miR-125a target genes among differentially expressed genes has identified likely target genes and indicates that integrating global miRNA and mRNA expression data may give further insights into miRNA-mediated regulation of gene expression. </p> |
| first_indexed | 2024-03-06T23:58:28Z |
| format | Journal article |
| id | oxford-uuid:75108e34-dbd1-4547-bd83-016976ebb573 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:58:28Z |
| publishDate | 2009 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:75108e34-dbd1-4547-bd83-016976ebb5732022-03-26T20:07:14ZMicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 DiabetesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:75108e34-dbd1-4547-bd83-016976ebb573EnglishSymplectic Elements at OxfordBioMed Central2009Herrera, BLockstone, HTaylor, JWills, QKaisaki, PBarrett, ACamps, CFernandez, CRagoussis, JGauguier, DMcCarthy, MLindgren, C <p style="text-align:justify;"> <b>Background:</b> MicroRNAs (miRNAs) are non-coding RNA molecules involved in post-transcriptional control of gene expression of a wide number of genes, including those involved in glucose homeostasis. Type 2 diabetes (T2D) is characterized by hyperglycaemia and defects in insulin secretion and action at target tissues. We sought to establish differences in global miRNA expression in two insulin-target tissues from inbred rats of spontaneously diabetic and normoglycaemic strains.<br/><br/> <b>Methods</b> We used a miRNA microarray platform to measure global miRNA expression in two insulin-target tissues: liver and adipose tissue from inbred rats of spontaneously diabetic (Goto-Kakizaki [GK]) and normoglycaemic (Brown-Norway [BN]) strains which are extensively used in genetic studies of T2D. MiRNA data were integrated with gene expression data from the same rats to investigate how differentially expressed miRNAs affect the expression of predicted target gene transcripts.<br/><br/> <b>Results:</b> The expression of 170 miRNAs was measured in liver and adipose tissue of GK and BN rats. Based on a p-value for differential expression between GK and BN, the most significant change in expression was observed for miR-125a in liver (FC = 5.61, P = 0.001, P adjusted = 0.10); this overexpression was validated using quantitative RT-PCR (FC = 13.15, P = 0.0005). MiR-125a also showed over-expression in the GK vs. BN analysis within adipose tissue (FC = 1.97, P = 0.078, P adjusted = 0.99), as did the previously reported miR-29a (FC = 1.51, P = 0.05, P adjusted = 0.99). In-silico tools assessing the biological role of predicted miR-125a target genes suggest an over-representation of genes involved in the MAPK signaling pathway. Gene expression analysis identified 1308 genes with significantly different expression between GK and BN rats (P adjusted < 0.05): 233 in liver and 1075 in adipose tissue. Pathways related to glucose and lipid metabolism were significantly over-represented among these genes. Enrichment analysis suggested that differentially expressed genes in GK compared to BN included more predicted miR-125a target genes than would be expected by chance in adipose tissue (FDR = 0.006 for up-regulated genes; FDR = 0.036 for down-regulated genes) but not in liver (FDR = 0.074 for up-regulated genes; FDR = 0.248 for down-regulated genes).<br/><br/> <b>Conclusion:</b> MiR-125a is over-expressed in liver in hyperglycaemic GK rats relative to normoglycaemic BN rats, and our array data also suggest miR-125a is over-expressed in adipose tissue. We demonstrate the use of in-silico tools to provide the basis for further investigation of the potential role of miR-125a in T2D. In particular, the enrichment of predicted miR-125a target genes among differentially expressed genes has identified likely target genes and indicates that integrating global miRNA and mRNA expression data may give further insights into miRNA-mediated regulation of gene expression. </p> |
| spellingShingle | Herrera, B Lockstone, H Taylor, J Wills, Q Kaisaki, P Barrett, A Camps, C Fernandez, C Ragoussis, J Gauguier, D McCarthy, M Lindgren, C MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes |
| title | MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes |
| title_full | MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes |
| title_fullStr | MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes |
| title_full_unstemmed | MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes |
| title_short | MicroRNA-125a is over-expressed in insulin target tissues in a spontaneous rat model of Type 2 Diabetes |
| title_sort | microrna 125a is over expressed in insulin target tissues in a spontaneous rat model of type 2 diabetes |
| work_keys_str_mv | AT herrerab microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT lockstoneh microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT taylorj microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT willsq microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT kaisakip microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT barretta microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT campsc microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT fernandezc microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT ragoussisj microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT gauguierd microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT mccarthym microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes AT lindgrenc microrna125aisoverexpressedininsulintargettissuesinaspontaneousratmodeloftype2diabetes |