HNF-4α regulated miR-122 contributes to development of gluconeogenesis and lipid metabolism disorders in Type 2 diabetic mice and in palmitate-treated HepG2 cells

Wei, Shengnan; Zhang, Ming; Yu, Yang; Hai, Xue; Lan, Xiaoxin; Liu, Shuping; Hatch, Grant M.; Chen, Li

doi:10.1016/j.ejphar.2016.08.038

Cited by 43 publications

(31 citation statements)

References 46 publications

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“…Evidence of G6PC3 and ALDOA as putative targets has been confirmed using luciferase reporter [19]. Our data coordinate with prevails studies indicating that mir-122 regulates the expression of the mRNAs and proteins related to G6PC3 [20], ALDOA [21] and CS [22] in cell cultures.…”

Section: Resultssupporting

confidence: 85%

“…They also found that mir-122 is up-regulated in cancer-secreted enclosed vesicles and transfers to normal cells to suppress CS expression and glucose utilization in these cells [22]. Furthermore, G6PC3 is a gluconeogenic enzyme that can be stimulated by mir-122 reduction to contribute to gluconeogenesis [20, 31]. All of these studies demonstrate that mir-122 is down-regulated in hypoxia and can stimulate intracellular glucose by up-regulating G6PC3 and ALDOA regardless of whether it is stimulated by glycolysis or by gluconeogenic factors.…”

Section: Discussionmentioning

confidence: 99%

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G6PC3, ALDOA and CS induction accompanies mir-122 down-regulation in the mechanical asphyxia and can serve as hypoxia biomarkers

Zeng

et al. 2016

Oncotarget

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Hypoxia influences different cellular biological processes. To reveal the dynamics of hypoxia's effects on miRNA regulation in vivo, we examined the expression levels of all miRNAs in human brain and heart specimens from cases of mechanical asphyxia compared with those from cases of craniocerebral injury and hemorrhagic shock. We further validated differently expressed miRNAs in another 84 human specimens and rat models. We found that mir-122 was significantly down-regulated and that its putative targets G6PC3, ALDOA and CS were increased in the brain and cardiac tissues in cases of mechanical asphyxia compared with craniocerebral injury and hemorrhagic shock. Our data indicate that mir-122 and its targets G6PC3, ALDOA and CS play roles in the hypoxia responses that regulate glucose and energy metabolism and can serve as hypoxia biomarkers.

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Section: Resultssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

G6PC3, ALDOA and CS induction accompanies mir-122 down-regulation in the mechanical asphyxia and can serve as hypoxia biomarkers

Zeng

et al. 2016

Oncotarget

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“…There are a number of studies investigating the relationship of miRNA and diabetes based on animal models and cell line systems [99,100,101,102,103]. These studies provide valuable information, but in the current analysis, we did not include these studies because the model systems, either in vivo or in vitro, can only reflect very limited aspects of the T2DM pathology.…”

Section: Discussionmentioning

confidence: 99%

A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

Ding

Liang

et al. 2017

IJMS

109

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MicroRNAs (miRNAs) are small noncoding RNAs that modulate the cellular transcriptome at the post-transcriptional level. miRNA plays important roles in different disease manifestation, including type 2 diabetes mellitus (T2DM). Many studies have characterized the changes of miRNAs in T2DM, a complex systematic disease; however, few studies have integrated these findings and explored the functional effects of the dysregulated miRNAs identified. To investigate the involvement of miRNAs in T2DM, we obtained and analyzed all relevant studies published prior to 18 October 2016 from various literature databases. From 59 independent studies that met the inclusion criteria, we identified 158 dysregulated miRNAs in seven different major sample types. To understand the functional impact of these deregulated miRNAs, we performed targets prediction and pathway enrichment analysis. Results from our analysis suggested that the altered miRNAs are involved in the core processes associated with T2DM, such as carbohydrate and lipid metabolisms, insulin signaling pathway and the adipocytokine signaling pathway. This systematic survey of dysregulated miRNAs provides molecular insights on the effect of deregulated miRNAs in different tissues during the development of diabetes. Some of these miRNAs and their mRNA targets may have diagnostic and/or therapeutic utilities in T2DM.

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“…Wei et al [27] examined the role of miR-122 in regulating lipid metabolism. They found that miR-122 and hepatocyte nuclear factor-4 α (HNF-4 α ) expression were increased in diabetic mice and in palmitate-treated HepG2 cells.…”

Section: Basic Research On Micrornas In Cvd In Diabetesmentioning

confidence: 99%

“…HNF-4 α is a nuclear receptor protein involved in liver development that modulates miR-122 levels in mouse liver [28]. HNF-4 α and miR-122 expression in HepG2 cells upregulated the expression of SREBP-1 and FAS, which control cellular cholesterol homeostasis, and activated the genes that control fatty acid, cholesterol, and triglyceride synthesis [27] (Figure 3). …”

Section: Basic Research On Micrornas In Cvd In Diabetesmentioning

confidence: 99%

MicroRNAs and Cardiovascular Disease in Diabetes Mellitus

Ding

Sun

2017

BioMed Research International

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Cardiovascular disease (CVD) is the major macrovascular complication of diabetes mellitus. Recently, although CVD morbidity and mortality have decreased as a result of comprehensive control of CVD risk factors, CVD remains the leading cause of death of patients with diabetes in many countries, indicating the potential underlying pathophysiological mechanisms. MicroRNAs are a class of noncoding, single-stranded RNA molecules that are involved in β-cell function, insulin secretion, insulin resistance, skeletal muscle, and adipose tissue and which play an important role in glucose homeostasis and the pathogenesis of diabetic complications. Here, we review recent progress in research on microRNAs in endothelial cell and vascular smooth muscle cell dysfunction, macrophage and platelet activation, lipid metabolism abnormality, and cardiomyocyte repolarization in diabetes mellitus. We also review the progress of microRNAs as potential biomarkers and therapeutic targets of CVD in patients with diabetes.

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HNF-4α regulated miR-122 contributes to development of gluconeogenesis and lipid metabolism disorders in Type 2 diabetic mice and in palmitate-treated HepG2 cells

Cited by 43 publications

References 46 publications

G6PC3, ALDOA and CS induction accompanies mir-122 down-regulation in the mechanical asphyxia and can serve as hypoxia biomarkers

G6PC3, ALDOA and CS induction accompanies mir-122 down-regulation in the mechanical asphyxia and can serve as hypoxia biomarkers

A Systematic Study of Dysregulated MicroRNA in Type 2 Diabetes Mellitus

MicroRNAs and Cardiovascular Disease in Diabetes Mellitus

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