Circulating MiRNAs of ‘Asian Indian Phenotype’ Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes

Prabu, Paramasivam; Rome, Sophie; Chandrakumar, Sathishkumar; Sivasubramanian, Aravind; Balakumar, Mahalingam; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

doi:10.1371/journal.pone.0128372

Cited by 65 publications

(59 citation statements)

References 45 publications

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“…; evaluation of miRNA concentrations before and after exercise, metformine treatment or bypass surgery). These studies involved both Caucasian [26–39] and Asian populations [40–51]. …”

Section: Resultsmentioning

confidence: 99%

Diagnostic Value of Cell-free Circulating Micrornas for Obesity and Type 2 Diabetes: A Meta-analysis

Villard¹,

Marchand²

2015

J Mol Biomark Diagn

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110

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Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder worldwide. Because of population aging and increasing trends toward obesity and sedentary lifestyles, the number of affected individuals is increasing at worrisome rates. While both environmental and genetic factors are known to contribute to the development of T2DM, continuous research is needed to identify specific biomarkers that could aid both in prevention of the disease and development of newer therapeutic options. Circulating miRNAs are considered as potential biomarkers because they are stable and resistant to degradation by blood RNAses and are modified under different pathophysiological conditions. In this study we carried out a systematic electronic search on PubMed to retrieve all articles that have investigated circulating miRNAs for diagnosing obesity andT2DM in human. We also included lifestyle intervention studies known to be highly effective in delaying onset of diabetes, and studies analyzing the effect of bariatric surgery and anti-diabetic treatment. A total of 26 studies were enrolled in the global meta-analysis. Candidate miRNAs were defined as those reported in at least 2 studies with same direction of differential expression. Ten miRNAs altered in blood of patients suffering fromT2DM were identified (increased: miR-320a, miR-142-3p, miR-222, miR-29a, miR-27a, miR-375; decreased: miR-197, miR-20b, miR-17, miR-652) and 7 miRNAs in blood of obese subjects were identified (increased: miR-142-3p, miR-140-5p, miR-222; decreased:miR-21-5p, miR-221-3p, miR-125-5p, mir-103-5p). Both obese and T2DM patients had elevated concentrations of miR-142-3p and miR-222. MiRNAs target genes were predicted and their cellular functions are discussed in relation with the pathologies. Although a significant number of studies were taken into account in this review, we found a strong discrepancy between miRNA detection and quantification indicating that many of pre-analytical variables have yet to be normalized. Pre-analytical and analytical challenges are also discussed.

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“…; evaluation of miRNA concentrations before and after exercise, metformine treatment or bypass surgery). These studies involved both Caucasian [26–39] and Asian populations [40–51]. …”

Section: Resultsmentioning

confidence: 99%

Diagnostic Value of Cell-free Circulating Micrornas for Obesity and Type 2 Diabetes: A Meta-analysis

Villard¹,

Marchand²

2015

J Mol Biomark Diagn

Self Cite

110

View full text Add to dashboard Cite

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“…These serum constituents were complex. In addition, diabetic subjects are characterized by an altered circulating miRNA profile [25], metabolic profile and certain other profiles. A diabetic VEC model was established using this method.…”

Section: Discussionmentioning

confidence: 99%

Effect of the Diabetic Environment On the Expression of MiRNAs in Endothelial Cells: Mir-149-5p Restoration Ameliorates the High Glucose-Induced Expression of TNF-α and ER Stress Markers

Yuan

Chen

et al. 2017

Cell Physiol Biochem

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Background/Aims: This study aimed to screen microRNAs and their corresponding target genes that are associated with vascular injury in type two diabetes mellitus (T2DM), investigate the effects of differentially expressed miRNAs and their target genes on high glucose-induced vascular injury and establish the mechanism underlying these effects. Methods: A high-throughput digital gene expression (DGE) sequencing was performed to sequence microRNAs (miRNAs) and messenger RNAs (mRNAs) and determine their differential expression in human umbilical vein endothelial cells (HUVECs) incubated with serum samples from patients with T2DM and healthy volunteers. The HUVECs were transfected with si-TNF-α (tumor necrosis factor α) and a miR-149-5p inhibitor or mimic in vitro and then treated with normal or high glucose. The relative content of nitric oxide (NO) in the cells was detected using the Griess Reagent System. The mRNA and protein expression of endothelial nitric oxide synthase (eNOS) were determined by qRT-PCR and Western blotting. The content of endothelin-1 (ET-1), von Willebrand factor (vWF), and intercellular adhesion molecular-1 (ICAM-1) were detected using an enzyme-linked immunosorbent assay (ELISA) kit. Apoptosis was determined by flow cytometry using the Annexin V/PI apoptosis detection kit. The mRNA and protein expression levels of ER stress (ERS) markers were determined by qRT-PCR and Western blotting. Results: Based on the high-energy sequencing and in vitro pre-experiment studies, we determined that miR-149-5p and TNF-α were a differentially expressed mRNA/miRNA pair in T2DM with vascular injury. The luciferase reporter assay results demonstrated that miR-149-5p could directly target TNF-α. The upregulation of miR-149-5p reduced the high glucose-induced dysfunction in the HUVECs by significantly decreasing the levels of ET-1, vWF, and ICAM-1 and increasing the level of NO and the expression of eNOS. Additionally, we found that miR-149-5p can improve cell injury and reduce apoptosis by restoring the ameliorated high glucose-induced expression of ERS markers. Conclusion: TNF-α and miR-149-5p were differentially expressed in T2DM vascular endothelial injury. The over-expression of miR-149-5p ameliorates the high glucose-induced injury in the HUVECs by regulating the expression of TNF-α and ERS markers.

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“…Studies conducted in the Indian (serum) and Spanish (plasma) population report downregulation of miR-423-5p in T2DM subjects [79,98]. Table 3 do not report the same set of miRNAs as prognostic/diagnostic biomarkers for T2DM in different populations.…”

Section: Mir-423-5pmentioning

confidence: 97%

“…While on the one hand, a recent study from the Indian population reports an upregulation of miR-130-3b in T2DM subjects from serum samples [98]; another study from a Spanish cohort reported its downregulation in plasma samples [79].…”

Section: Mir130b-3pmentioning

confidence: 99%

“…A lot of progress has been made in the understanding of the biogenesis, activity and the function of miRNAs. Several miRNAs show changes in their expression (high and low) and these changes in expression [81] Plasma Spain Down [79] Plasma Chinese Han Down [80] Plasma Bruneck (Italy) Down [66] miR-130b-3p Serum Indian Up [98] Plasma Spain Down [79] miR-144 Plasma Swedish and Iraqi Up [86] Blood Asian Up [73] miR-146a Serum Chinese Han Down [72] Plasma Chinese Han Up [74] Serum China Up [75] PBMCs Indian Down [70] Blood Asian Up [73] miR-192 Serum Chinese Han Down [72] Plasma Spain Down [79] miR-375 Serum Japanese Up [84] Plasma Chinese Kazak Up [85] Serum China Up [75] miR-423-5p Serum Indian Down [98] Plasma Spain Down [79] has been linked to several diseases including T2DM in various population studies. Their presence in extracellular fluids in stable forms has led to the idea of using them as biomarkers for a variety of diseases.…”

Section: Important Issues/challenges In Assessing Circulating Mirnasmentioning

confidence: 99%

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MIRNAS: Early Prognostic Biomarkers for Type 2 Diabetes Mellitus?

et al. 2015

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Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and is associated with peripheral insulin resistance. The currently used therapies aim to delay progression of T2DM. Their efficacy could drastically be improved if implemented at earlier stages. Classical diagnostic markers (blood glucose and HbA1C) are generally detected once metabolic imbalance has already set in. Therefore, development of biomarkers for early diagnosis would help identify individuals at risk for developing T2DM. Along with genetic predisposition, epigenetics also plays a major role in T2DM development. In this review, we discuss the potential role of early diagnostic markers such as circulating miRNAs, studies done so far and challenges to be considered while taking into account the novel role of miRNAs as prognostic biomarkers.

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Circulating MiRNAs of ‘Asian Indian Phenotype’ Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes

Cited by 65 publications

References 45 publications

Diagnostic Value of Cell-free Circulating Micrornas for Obesity and Type 2 Diabetes: A Meta-analysis

Diagnostic Value of Cell-free Circulating Micrornas for Obesity and Type 2 Diabetes: A Meta-analysis

Effect of the Diabetic Environment On the Expression of MiRNAs in Endothelial Cells: Mir-149-5p Restoration Ameliorates the High Glucose-Induced Expression of TNF-α and ER Stress Markers

MIRNAS: Early Prognostic Biomarkers for Type 2 Diabetes Mellitus?

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