Plasma miR-17, miR-20a, miR-20b and miR-122 as potential biomarkers for diagnosis of NAFLD in type 2 diabetes mellitus patients

Ye, Dan; Zhang, Tianbao; Lou, Guohua; Xu, Weiwei; Dong, Fengqin; Chen, Guoping; Liu, Yanning

doi:10.1016/j.lfs.2018.07.029

Cited by 69 publications

(60 citation statements)

References 37 publications

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“…Then, the relative level of miR-122 was found to be increased significantly, and that of IGF-1R protein, conversely, decreased in the liver of DM rats. Recent studies have indicated that accentuated miRNA dysregulation was found in impaired glucose tolerance and diabetes subjects with an increased level of miR-122 (de Candia et al, 2017;Ye et al, 2018). These previous studies and our in vivo data suggest that miR-122 may be involved in T2D and hepatic IR.…”

Section: Discussionsupporting

confidence: 81%

See 1 more Smart Citation

Regulation of insulin resistance by targeting the insulin‐like growth factor 1 receptor with microRNA‐122‐5p in hepatic cells

Dong

Hou

Liu

et al. 2019

Cell Biology International

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Insulin resistance (IR) is a common etiology of type 2 diabetes (T2D) defined by a state of decreased reactivity to insulin in multiple organs, such as the liver. This study aims to investigate how microRNA-122-5p (miR-122) regulates the hepatic IR in vitro. We first found that the miR-122 level was upregulated in the liver of rats fed with a high-fat diet and injected with streptozotocin (T2D rats), while the expression level of insulin-like growth factor 1 receptor (IGF-1R), a potential target of miR-122, was downregulated in the diabetic liver. In vitro, glucosamine-induced IR was introduced in HepG2 hepatic cells, and the levels of miR-122 and IGF-1R were further assessed. An increase of miR-122 level and a decrease of IGF-IR level were observed in IR hepatic cells, which was the same as that in the diabetic liver. Results of the luciferase reporter assay validated IGF-1R as a direct target of miR-122. Moreover, in IR HepG2 cells, antagonizing miR-122 with its specific inhibitor enhanced glucose uptake and suppressed the expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase, two key enzymes in regulating gluconeogenesis. Such alterations induced by the miR-122 inhibitor in IR hepatic cells were impaired when IGF-1R was simultaneously knocked down. In addition, the PI3K/Akt pathway was deactivated in IR cells, and then reactivated with miR-122 inhibitor transfection. In conclusion, our study demonstrates that miR-122 is able to regulate IR in hepatic cells by targeting IGF-1R.

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Section: Discussionsupporting

confidence: 81%

“…(C) miR-122 relative expression. Recent studies have indicated that accentuated miRNA dysregulation was found in impaired glucose tolerance and diabetes subjects with an increased level of miR-122 (de Candia et al, 2017;Ye et al, 2018). Data are presented as the mean ± standard deviation.…”

Section: Discussionmentioning

confidence: 99%

Regulation of insulin resistance by targeting the insulin‐like growth factor 1 receptor with microRNA‐122‐5p in hepatic cells

Dong

Hou

Liu

et al. 2019

Cell Biology International

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“…Indeed, in adults, miR-122 seems to be a key regulator of cholesterol and fatty acid metabolism in the liver [30], and it was associated with insulin resistance, obesity, metabolic syndrome, type 2 diabetes, and adverse lipid profile [31]. Moreover, in adults, high levels of circulating miR-122 have also been associated with increased concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), triglycerides, and lower HDL-cholesterol levels, as well as with hepatic steatosis and the degree and progression of NAFLD [31][32][33][34]. In agreement with these results, Brandt et al observed that miR-122 circulating (plasma or serum) levels were higher in children with NAFLD than in non-NAFLD overweight children and that miR-122 concentrations were associated with higher liver enzyme levels (i.e., ALT, AST, and GGT) [35].…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNAs as Biomarkers of Obesity and Obesity-Associated Comorbidities in Children and Adolescents: A Systematic Review

Osés

Sanchez²,

Baquedano

et al. 2019

Nutrients

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Early detection of obesity and its associated comorbidities in children needs priority for the development of effective therapeutic intervention. Circulating miRNAs (microRNAs) have been proposed as biomarkers for obesity and its comorbidities; therefore, we conducted a systematic review to summarize results of studies that have quantified the profile of miRNAs in children and adolescents with obesity and/or associated disorders. Nine studies aiming to examine differences in miRNA expression levels between children with normal weight and obesity or between obese children with or without cardiometabolic diseases were included in this review. We identified four miRNAs overexpressed in obesity (miR-222, miR-142–3, miR-140-5p, and miR-143) and two miRNAs (miR-122 and miR-34a) overexpressed in children with obesity and nonalcoholic fatty liver disease (NAFLD) and/or insulin resistance. In conclusion, circulating miRNAs are promising diagnostic biomarkers of obesity-associated diseases such as NAFLD and type 2 diabetes already in childhood. However, more studies in children, using massive search technology and with larger sample sizes, are required to draw any firm conclusions.

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“…Down-regulated circulating miR-20a levels were associated with reduced hepatic glycogen synthesis. However, Dan et al reported that circulating miR-20a was up-regulated in T2DM patients with NAFLD complication 42 . The reason for the difference between their report and our results is unclear at present.…”

Section: Discussionmentioning

confidence: 98%

Association of circulating miR-20a, miR-27a, and miR-126 with non-alcoholic fatty liver disease in general population

Ando

Yamazaki

Yamada

et al. 2019

Sci Rep

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Non-alcoholic fatty liver disease (NAFLD) is closely associated with obesity, metabolic syndrome, and type II diabetes mellitus. Recently, circulating microRNAs (miRNAs) have been proposed as useful disease biomarkers. We examined whether circulating miRNAs, such as miR-20a, miR-27a, and miR-126, were useful biomarkers for NAFLD. We conducted a cross-sectional analysis of 527 subjects aged 39 years or older who had undergone a health examination in the Yakumo Study. Of the residents, 92 were diagnosed with NAFLD using a registered medical sonographer. Serum miR-20a, miR-27a and miR-126 levels were measured by quantitative real-time PCR. We then calculated the odds ratios for serum miRNA level changes according to the severity of NAFLD using normal liver status as the reference group. Serum levels of miR-20a and 27a, but not miR-126, were significantly lower in NAFLD subjects than normal subjects. Serum miR-20a and miR-27a levels were significantly lower in both male and female severe NAFLD subjects. Logistic regression analysis showed a significant relationship between low circulating miR-20a and 27a levels and severe NAFLD. Down-regulated circulating miR-20a and 27a levels were significantly associated with severe NAFLD in the general population. Circulating miR-20a and miR-27a may be useful biomarkers for severe NAFLD.Non-alcoholic fatty liver disease (NAFLD) currently represents one of the most common diseases worldwide. The global prevalence of NAFLD has increased from 20 to 30% over the past two decades. Although 80-90% of NAFLD patients have simple liver steatosis, the remaining 10-20% of patients have non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis or even hepatocellular carcinoma 1 . Furthermore, NAFLD is closely associated with metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD) 2-4 .

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Plasma miR-17, miR-20a, miR-20b and miR-122 as potential biomarkers for diagnosis of NAFLD in type 2 diabetes mellitus patients

Cited by 69 publications

References 37 publications

Regulation of insulin resistance by targeting the insulin‐like growth factor 1 receptor with microRNA‐122‐5p in hepatic cells

Regulation of insulin resistance by targeting the insulin‐like growth factor 1 receptor with microRNA‐122‐5p in hepatic cells

Circulating miRNAs as Biomarkers of Obesity and Obesity-Associated Comorbidities in Children and Adolescents: A Systematic Review

Association of circulating miR-20a, miR-27a, and miR-126 with non-alcoholic fatty liver disease in general population

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