A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

He, Yuqing; Ding, Yuanlin; Liang, Buqing; Lin, Juanjuan; Kim, Taek‐Kyun; Yu, Haibing; Hang, Hanwei; Wang, Kai

doi:10.3390/ijms18030456

Cited by 107 publications

(101 citation statements)

References 102 publications

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“…MicroRNAs are small noncoding RNAs composed of 21-23 nucleotides that act as the key regulators of gene expression and biological processes (He et al, 2017). Previous studies have *Author for correspondence: Shirin Shahbazi, Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.…”

Section: Introductionmentioning

confidence: 99%

Plasma miR-126 levels and its genomic polymorphism SNP rs4636297 in Type 2 diabetes

Rezai

Shahbazi

Mansournia

2020

APJMBB

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Since the variation of microRNAs expression has been described in type2 diabetes, we aimed to evaluate the plasma levels of miR-126 with known roles in the angiogenesis. Genomic polymorphism of miR-126 (SNP rs4636297) was also assessed as it is involved in the processing of pri-miR-126 to mature microRNA.Genotyping of the SNP rs4636297 was carried out by PCR-RFLP using HaeII enzyme. Real-time PCR assay was applied to assess miR-126 expression, which the fold change in gene expression was calculated by the Relative Expression Software Tool (REST). Data analysis was performed using exact-like logistic regression, Fisher exact test and the elrm package with the R software. Our data indicated that the group with BMI greater than 30 was at greater risk of diabetes (odds ratio=14.4, p value=0.00), compared with the BMI=19-25. The mean fold decrease in miR-126 gene expression in diabetic samples relative to normal samples was 0.653 (95% confidence interval: 0.012 - 18.765). All patients with the lowest levels of miR-126, had experienced diabetic complications. Considering the AA genotype as the reference, the odds ratio of diabetic complications for the GG and AG genotype were 1.2 and 1.43, respectively. miR-126 is one of the key factors in predisposition to diabetes and diabetic complication. Since the lowest expression of miR-126 leads to the diabetic complications it can be concluded that genetic predisposing factors should be considered in the management and treatment of Type 2 diabetes.

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Section: Introductionmentioning

confidence: 99%

Plasma miR-126 levels and its genomic polymorphism SNP rs4636297 in Type 2 diabetes

Rezai

Shahbazi

Mansournia

2020

APJMBB

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“…[21][22][23] Of the 57 miRNAs showing concentration differences between the progressor and non-progressor groups, 26 of them (miR-10b-5p, miR-144-3p, miR-451a-5p, miR-192-5p, miR-125b-5p, miR-101-5p, miR-122-5p, miR-150-5p, miR-17-3p, miR-193a-5p, miR-193b-3p, miR-29c-5p, miR-320a-3p, miR-320b-3p, miR-550a-3p, miR-100-5p, miR-10a-5p, miR-181a-3p, miR-190a-5p, miR-136-5p, miR-375-3p, miR-487b-3p, miR-7-5p, miR-210-3p, miR-378a-3p, and miR-99a-5p) have been previously described as being associated with T2DM based on our recent meta-analysis of the field. 10 We selected 14 miRNAs for qRT-PCR validation and were able to confirm the concentration changes for 10 of these miRNAs (miR-122-5p, miR-127-5p, miR-192-5p, miR-210-3p, miR-3200-3p, miR-375-3p, miR-376b-3p, miR-4532-5p, and miR-660-3p, and miR-7641-3p). Some miRNAs could not be verified with qRT-PCR, probably due to the specific qPCR platform used and high-false negative rate associated with qRT-PCR as previously reported.…”

Section: Log 2 Fc (> 15 Fold Change P-value B-h Fdrmentioning

confidence: 99%

Circulating RNAs as predictive markers for the progression of type 2 diabetes

Ghai

Baxter

et al. 2019

J Cellular Molecular Medi

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Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of diabetes in the USA, thus, the identification of biomarkers that could be used to predict the progression from prediabetes to T2DM would be greatly beneficial. Recently, circulating RNA including microRNAs (miRNAs) present in various body fluids have emerged as potential biomarkers for various health conditions, including T2DM. Whereas studies that examine the changes of miRNA spectra between healthy controls and T2DM individuals have been reported, the goal of this study is to conduct a baseline comparison of prediabetic individuals who either progress to T2DM, or remain prediabetic. Using an advanced small RNA sequencing library construction method that improves the detection of miRNA species, we identified 57 miRNAs that showed significant concentration differences between progressors (progress from prediabetes to T2DM) and non‐progressors. Among them, 26 have been previously reported to be associated with T2DM in either body fluids or tissue samples. Some of the miRNAs identified were also affected by obesity. Furthermore, we identified miRNA panels that are able to discriminate progressors from non‐progressors. These results suggest that upon further validation these miRNAs may be useful to predict the risk of conversion to T2DM from prediabetes.

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“…It is also showed that miR-335 upregulation promoted defective initiation of insulin vesicles, resulting in impaired insulin secretion [27]. As for the part of miR-765 regulating diabetes, a study observed an enrichment of miR-765 in T2D [28]. To grasp more molecular evidence for T2D development, we here examined the role of miR-765 in this area as well as its interaction with PDX1.…”

Section: Introductionmentioning

confidence: 98%

miR-765 Impairs Pancreatic β-cell Function by Targeting PDX1 in type 2 Diabetes

Li¹,

Wang²,

Li³

et al. 2020

Preprint

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Background: Type 2 diabetes (T2D) is highly connected with the defect in insulin secretion of pancreatic β-cells, which has been developing into a severe public health problem.Methods: Here, we first detected expression of PDX1 and miR-765 in peripheral blood from 40 patients with T2D and 40 healthy volunteers. INS-1E cells (pancreatic β-cell line) were cultured as experimental model. For glucose induction, we incubated INS-1E cells with 11 mM glucose as control group and INS-1E cells with 25 mM glucose as T2D model group. For target relationship verification, we performed Luciferase reporter assay. Generally, we utilized qRT-PCR (quantitative real-time PCR), western blotting, insulin secretion detection, CCK-8, and flow cytometry in this study.Results: The expression level of PDX1 was dramatically lower in peripheral blood from T2D patients than healthy volunteers, while miR-765 exhibited an opposite result. PDX1 expression level had an inverse correlation with blood glucose level of T2D patients whereas miR-765 exhibited a positive correlation. Furthermore, PDX1 improved insulin secretion, cell viability, and restrained cell apoptosis of INS-1E cells. PDX1 was identified as a target of miR-765 which was observed to reduce insulin secretion, cell viability, and induce cell apoptosis of INS-1E cells.Conclusions: Taken together, we confirmed that miR-765 could cause detrimental effect on pancreatic β-cell survival and function by targeting and repressing PDX1 in T2D.

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A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

Cited by 107 publications

References 102 publications

Plasma miR-126 levels and its genomic polymorphism SNP rs4636297 in Type 2 diabetes

Plasma miR-126 levels and its genomic polymorphism SNP rs4636297 in Type 2 diabetes

Circulating RNAs as predictive markers for the progression of type 2 diabetes

miR-765 Impairs Pancreatic β-cell Function by Targeting PDX1 in type 2 Diabetes

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