TY - JOUR
T1 - MicroRNA biomarkers target genes and pathways associated with type 2 diabetes
AU - Kariuki, Dorian
AU - Aouizerat, Bradley E.
AU - Asam, Kesava
AU - Kanaya, Alka M.
AU - Zhang, Li
AU - Florez, Jose C.
AU - Flowers, Elena
N1 - Funding Information:
This study was supported by the National Institute of Diabetes and Digestive and Kidney Disease grant number R01DK124228 and R01DK124228-02S1. Biospecimens used in this study were provided under approval X01DK115999. Dr. Kanaya is supported by National Heart Lung, and Blood Institute of the National Institutes of Health grant number K24HL112827.
Funding Information:
The Diabetes Prevention Program (DPP) was conducted by the DPP Research Group and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the General Clinical Research Center Program, the National Institute of Child Health and Human Development (NICHD), the National Institute on Aging (NIA), the Office of Research on Women’s Health, the Office of Research on Minority Health, the Centers for Disease Control and Prevention (CDC), and the American Diabetes Association. The data and biospecimens from the DPP were supplied by the NIDDK Central Repository. This manuscript was not prepared under the auspices of the DPP and does not represent analyses or conclusions of the DPP Research Group, the NIDDK Central Repository, or the NIH.
Publisher Copyright:
© 2023
PY - 2023/9
Y1 - 2023/9
N2 - Aims/Hypothesis: Our prior analysis of the Diabetes Prevention Program study identified a subset of five miRNAs that predict incident type 2 diabetes. The purpose of this study was to identify mRNAs and biological pathways targeted by these five miRNAs to elucidate potential mechanisms of risk and responses to the tested interventions. Methods: Using experimentally validated data from miRTarBase version 8.0 and R (2021), we identified mRNAs with strong evidence to be regulated by individual or combinations of the five predictor miRNAs. Overrepresentation of the mRNA targets was assessed in pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation database. Results: The five miRNAs targeted 167 pathways and 122 mRNAs. Nine of the pathways have known associations with type 2 diabetes: Insulin signaling, Insulin resistance, Diabetic cardiomyopathy, Type 2 diabetes, AGE-RAGE signaling in diabetic complications, HIF-1 signaling, TGF-beta signaling, PI3K/Akt signaling, and Adipocytokine signaling pathways. Vascular endothelial growth factor A (VEGFA) has prior genetic associations with risk for type 2 diabetes and was the most commonly targeted mRNA for this set of miRNAs. Conclusions/Interpretation: These findings show that miRNA predictors of incident type 2 diabetes target mRNAs and pathways known to underlie risk for type 2 diabetes. Future studies should evaluate miRNAs as potential therapeutic targets for preventing and treating type 2 diabetes.
AB - Aims/Hypothesis: Our prior analysis of the Diabetes Prevention Program study identified a subset of five miRNAs that predict incident type 2 diabetes. The purpose of this study was to identify mRNAs and biological pathways targeted by these five miRNAs to elucidate potential mechanisms of risk and responses to the tested interventions. Methods: Using experimentally validated data from miRTarBase version 8.0 and R (2021), we identified mRNAs with strong evidence to be regulated by individual or combinations of the five predictor miRNAs. Overrepresentation of the mRNA targets was assessed in pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation database. Results: The five miRNAs targeted 167 pathways and 122 mRNAs. Nine of the pathways have known associations with type 2 diabetes: Insulin signaling, Insulin resistance, Diabetic cardiomyopathy, Type 2 diabetes, AGE-RAGE signaling in diabetic complications, HIF-1 signaling, TGF-beta signaling, PI3K/Akt signaling, and Adipocytokine signaling pathways. Vascular endothelial growth factor A (VEGFA) has prior genetic associations with risk for type 2 diabetes and was the most commonly targeted mRNA for this set of miRNAs. Conclusions/Interpretation: These findings show that miRNA predictors of incident type 2 diabetes target mRNAs and pathways known to underlie risk for type 2 diabetes. Future studies should evaluate miRNAs as potential therapeutic targets for preventing and treating type 2 diabetes.
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U2 - 10.1016/j.diabres.2023.110868
DO - 10.1016/j.diabres.2023.110868
M3 - Article
C2 - 37543292
AN - SCOPUS:85167790078
SN - 0168-8227
VL - 203
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
M1 - 110868
ER -