The microRNA-29 Family Dictates the Balance Between Homeostatic and Pathological Glucose Handling in Diabetes and Obesity

Dooley, James; Garcia-Perez, Josselyn E.; Sreenivasan, Jayasree; Schlenner, Susan; Vangoitsenhoven, Roman; Papadopoulou, Aikaterini S.; Tian, Lei; Schönefeldt, Susann; Serneels, Lutgarde; Deroose, Christophe M.; Staats, Kim A.; Schueren, Bart Van der; Strooper, Bart De; McGuinness, Owen P.; Mathieu, Chantal; Liston, Adrian

doi:10.2337/db15-0770

Cited by 138 publications

(149 citation statements)

References 26 publications

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“…miR-29a-3p-deficient mice have dysregulated exocytosis, promoting diabetes after unfolded protein stress [41]. Increased glucose levels upregulated miR-29a-3p in rat and human islets, while miR-29a-3p inhibited glucose-stimulated insulin secretion and increased proliferation of INS-1E beta cells [42].…”

Section: Discussionmentioning

confidence: 99%

Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes

et al. 2017

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Aims/hypothesis MicroRNAs (miRNAs) are key regulators of gene expression and novel biomarkers for many diseases. We investigated the hypothesis that serum levels of some miRNAs would be associated with islet autoimmunity and/or progression to type 1 diabetes. Methods We measured levels of 93 miRNAs most commonly detected in serum. This retrospective cohort study included 150 autoantibody-positive and 150 autoantibody-negative family-matched siblings enrolled in the TrialNet Pathway to Prevention Study. This was a young cohort (mean age = 11 years), and most autoantibody-positive relatives were at high risk because they had multiple autoantibodies, with 39/150 (26%, progressors) developing type 1 diabetes within an average 8.7 months of follow-up. We analysed miRNA levels in relation to autoantibody status, future development of diabetes and OGTT C-peptide and glucose indices of disease progression. Results Fifteen miRNAs were differentially expressed when comparing autoantibody-positive/negative siblings (range −2.5 to 1.3-fold). but receiver operating characteristic (ROC) analysis indicated low specificity and sensitivity. Seven additional miRNAs were differentially expressed among autoantibody-positive relatives according to disease progression; ROC returned significant AUC values and identified miRNA cut-off levels associated with an increased risk of disease in both cross-sectional and survival analyses. Levels of several miRNAs showed significant correlations (r 0.22-0.55) with OGTT outcomes. miR-21-3p, miR-29a-3p and miR-424-5p had the most robust associations. Conclusions/interpretation Serum levels of selected miRNAs are associated with disease progression and confer additional risk of the development of type 1 diabetes in young autoantibody-positive relatives. Further studies, including longitudinal assessments, are warranted to further define miRNA biomarkers for prediction of disease risk and progression.

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Section: Discussionmentioning

confidence: 99%

Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes

et al. 2017

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“…In particular, both miR-29a and miR-29c serve as negative regulators of insulin signaling via phosphatidylinositol 3-kinase (PI-3K) regulation. Global or hepatic insufficiency of miR-29 retards obesity and dietinduced insulin resistance (Dooley et al, 2016). Moreover, miRNAs are directly linked to inflammation and adiposity.…”

Section: Noncoding Rnamentioning

confidence: 99%

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management

Zhang

Ren

2016

Pharmacology & Therapeutics

100

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“…Our study was aimed to link miRNA regulation with lipid overload and the immunoinflammatory mechanism of AS. Many recent studies have found that miR-29a was involved in numerous biological processes, including AS (Liu et al, 2017), hepatocellular carcinoma (Parpart et al, 2014), myocardial fibrosis (Dai et al, 2014), glucose handling (Dooley et al, 2016), and so on. Nowadays, researchers have found that plasma miR-29a was a new biomarker that could play a role in the pathophysiology of AS (Hulsmans and Holvoet, 2013;Huang et al, 2016;Liu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

ox‐LDL increases microRNA‐29a transcription through upregulating YY1 and STAT1 in macrophages

Jian

Dai

Yao

et al. 2017

Cell Biology International

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Macrophages and oxidized low-density lipoprotein (ox-LDL) have been verified playing vital roles in the pathogenesis of atherosclerosis (AS). Previous studies demonstrated that microRNA-29a (miR-29a) was upregulated in many atherogenic process and cells, thus acting as an important participant in AS. But the detailed regulation mechanism of miR-29a in AS has not been fully understood. In our study, we demonstrated a positive feedback loop of ox-LDL-SRA-miR-29a. Furthermore, we found that YY1 and STAT1 were upregulated in ox-LDL-stimulating macrophages followed by translocation in the nucleus and binding to the transcriptional promoter region of miR-29a, thus leading to the increase of miR-29a expression. In addition, we demonstrated that JAK1/2 signaling was involved in miR-29a upregulation. Finally, we found that miR-29a played important roles in the secretion of proinflammation factors and lipid uptake in macrophages. We uncovered the molecular mechanism and provide novel insights into the function and regulatory network of miR-29a expression regulated by ox-LDL in macrophages.

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The microRNA-29 Family Dictates the Balance Between Homeostatic and Pathological Glucose Handling in Diabetes and Obesity

Cited by 138 publications

References 26 publications

Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes

Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes

Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management

ox‐LDL increases microRNA‐29a transcription through upregulating YY1 and STAT1 in macrophages

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