MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting mitofusin-2

Zhang, Ying; Yang, Lei; Yuan-fu, Gao; Fan, Zhongmin; Cai, Xiaoyan; Liu, Meng‐Yuan; Guo, Xirong; Gao, Chunlin; Xia, Zhengkun

doi:10.1016/j.mce.2013.08.004

Cited by 84 publications

(75 citation statements)

References 36 publications

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“…Bucha et al illustrated that the increased expression of miR-214 could target Mfn2 [31]. Consistently, miR-106b targeted the 30 untranslated regions (30 UTRs) of Mfn2, and Mfn2 proteins were abundant at the post-transcriptional level so that miR-214 could regulate Mfn2 gene at the posttranscriptional level [15, 32]. Previous studies have shown that miR-214 was overexpressed in MSCs of mice, but the expression of Mfn2 was lower in hematopoietic stem cells [9, 33].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-214 Affects Fibroblast Differentiation of Adipose-Derived Mesenchymal Stem Cells by Targeting Mitofusin-2 during Pelvic Floor Dysfunction in SD Rats with Birth Trauma

Wu¹,

Jiang²,

Chen³

et al. 2017

Cell Physiol Biochem

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Background/Aims: This study investigated whether microRNA-214 (miR-214) targets mitofusin-2 (Mfn2) in the process of fibroblast differentiation of adipose-derived mesenchymal stem cells (ADMSCs) during pelvic floor dysfunction (PFD) in Sprague Dawley (SD) rats with birth trauma. Methods: The ADMSCs were isolated from 4-6 week male SD rats (n = 20) and were cultured and divided into the blank, miR-214 mimic negative control (NC), miR-214 mimic, miR-214 inhibitor NC, miR-214 inhibitor, empty vector, Mfn2 over-expression and miR-214 + Mfn2 over-expression groups. Fibroblast differentiation of ADMSCs was measured with immunocytochemistry and immunofluorescence methods. The expression of miR-214 and the mRNA and protein expression of Mfn2, FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ and Runx2 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. A dual-luciferase reporter assay was performed to confirm whether Mfn2 was the target gene of miR-214. Results: During ADMSC differentiation into fibroblasts, miR-214 expression was up-regulated, but the expression of Mfn2 was down-regulated. Fibroblast differentiation of ADMSCs was promoted in the miR-214 mimic group but was inhibited in the miR-214 inhibitor and Mfn2 over-expression groups. The expression of Mfn2 was decreased, but the expression of FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ or Runx2 was increased in the miR-214 mimic group; the miR-214 inhibitor group and Mfn2 over-expression group exhibited the opposite results. Mfn2 was the target gene of miR-214. Conclusions: The study provided strong evidence that miR-214 could promote fibroblast differentiation of ADMSCs by down-regulating Mfn2 to improve PFD in SD rats with birth trauma.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-214 Affects Fibroblast Differentiation of Adipose-Derived Mesenchymal Stem Cells by Targeting Mitofusin-2 during Pelvic Floor Dysfunction in SD Rats with Birth Trauma

Wu¹,

Jiang²,

Chen³

et al. 2017

Cell Physiol Biochem

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“…By direct targeting of mitofusin-2, a GTPase located in the mitochondrial outer membrane necessary for mitochondrial fusion, forced expression of miR-106b led to alteration of mitochondrial morphology and increased oxidative stress [61], mimicking some features characteristic of type 2 diabetes. Interestingly, inhibition of miR-106b increased mitochondrial abundance and alleviated mitochondrial dysfunction induced by TNF treatment [61]. Questions remains as to whether overexpression of miR-149 or inhibition of miR-106b alone in insulin resistant mature skeletal muscle is sufficient to maintain mitochondrial function and if so, to increase oxidative metabolism in type 2 diabetes.…”

Section: Mitochondrial Functions and Mirnasmentioning

confidence: 98%

“…In insulin resistant mice, miR-149 was downregulated, whereas its overexpression in mouse C2C12 cells increased mitochondrial biogenesis and oxidative capacities [19]. Expression of miR-106b was increased in T2D patients, as well as HFD-fed mice and its expression was induced by TNF and palmitate in cultured C2C12 cells [61,62].…”

Section: Mitochondrial Functions and Mirnasmentioning

confidence: 99%

microManaging glucose and lipid metabolism in skeletal muscle: Role of microRNAs

Massart

Katayama

Krook

2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…In humans, microarray-based analysis of miRNA expression in skeletal muscle of diabetic patients identified differential expression of 62 miRNAs, including miR-106b and miR-133a (19). Further studies showed that miR-106b targets mitofusin-2 (Mfn2) and downregulates its expression and contributes to insulin resistance in C2C12 myotubes (88). miR-133a is, with miR-1, the most abundant miRNA in skeletal muscle (44).…”

Section: Impact Of Mirna On Insulin Sensitivity In Skeletal Musclesmentioning

confidence: 99%

Biological roles of microRNAs in the control of insulin secretion and action

Caldérari

Diawara

Garaud

et al. 2017

Physiological Genomics

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microRNAs (miRNAs) are intracellular and circulating molecular components contributing to genome expression control through binding mRNA targets, which generally results in downregulated mRNA expression. One miRNA can target several mRNAs, and one transcript can be targeted by several miRNAs, resulting in complex fine-tuning of regulation of gene networks and signaling pathways. miRNAs regulate metabolism, adipocyte differentiation, pancreatic development, β-cell mass, insulin biosynthesis, secretion, and signaling, and their role in diabetes and obesity is emerging. Their pathophysiological effects are essentially dependent on cellular coexpression with their mRNA targets, which can show tissue-specific transcriptional responses to disease conditions and environmental challenges. Current knowledge of miRNA biology and their impact on the pathogenesis of diabetes and obesity is based on experimental data documenting miRNA expression generally in single tissue types that can be correlated with expression of target mRNAs to integrate miRNA in functional pathways and gene networks. Here we present results from the most significant studies dealing with miRNA function in liver, fat, skeletal muscle, and endocrine pancreas and their implication in diabetes and obesity

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MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12 myotubes by targeting mitofusin-2

Cited by 84 publications

References 36 publications

MicroRNA-214 Affects Fibroblast Differentiation of Adipose-Derived Mesenchymal Stem Cells by Targeting Mitofusin-2 during Pelvic Floor Dysfunction in SD Rats with Birth Trauma

MicroRNA-214 Affects Fibroblast Differentiation of Adipose-Derived Mesenchymal Stem Cells by Targeting Mitofusin-2 during Pelvic Floor Dysfunction in SD Rats with Birth Trauma

microManaging glucose and lipid metabolism in skeletal muscle: Role of microRNAs

Biological roles of microRNAs in the control of insulin secretion and action

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