Mitochondrial Activity in Human White Adipocytes Is Regulated by the Ubiquitin Carrier Protein 9/microRNA-30a Axis

Koh, Eun Hee; Chen, Yong; Bader, David A.; Hamilton, Mark; He, Bin; York, Brian; Kajimura, Shingo; McGuire, Sean E.; Hartig, Sean M.

doi:10.1074/jbc.m116.749408

Cited by 31 publications

(28 citation statements)

References 48 publications

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“…For example, Ubc9 (ubiquitin carrier protein 9) expression is regulated by miR-30a in human subcutaneous adipocytes [34]. miR-30a reduces IRF4 expression through specific binding with the 3′UTR, thereby suppressing the Th17 differentiation and preventing the full autoimmune encephalomyelitis development [35].…”

Section: Discussionmentioning

confidence: 99%

miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis

Zhang

Liu

et al. 2017

IJMS

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Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in idiopathic pulmonary fibrosis (IPF) regulation is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 is yet to be investigated. Additionally, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual-luciferase reporter assay system were used to identify the target gene of miR-30a, and cell transfection was utilized to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and miR-30a mimic and inhibitor transfection significantly reduced and increased the TET1 protein expression, respectively. Further experimentation verified that the TET1 siRNA interference could inhibit Drp-1 promoter hydroxymethylation. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit TET1 expression through base pairing with complementary sites in the 3 untranslated region to regulate Drp-1 promoter hydroxymethylation. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

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Section: Discussionmentioning

confidence: 99%

miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis

Zhang

Liu

et al. 2017

IJMS

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“…(128)(129)(130)(131)]. More recently, it was shown that miRNA30a controls Ubc9 levels in human subcutaneous adipocytes, with consequences for their mitochondrial activity (132). Another way to directly regulate the E2 catalytic activity is the previously-discussed transient disulfide bridge formed between the catalytic cysteines of the E1 and the E2 enzymes (94,95).…”

Section: E2 Regulationmentioning

confidence: 99%

SUMO conjugation – a mechanistic view

Pichler

Fatouros

Lee

et al. 2017

Biomolecular Concepts

218

223

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Abstract:The regulation of protein fate by modification with the small ubiquitin-related modifier (SUMO) plays an essential and crucial role in most cellular pathways. Sumoylation is highly dynamic due to the opposing activities of SUMO conjugation and SUMO deconjugation. SUMO conjugation is performed by the hierarchical action of E1, E2 and E3 enzymes, while its deconjugation involves SUMO-specific proteases. In this review, we summarize and compare the mechanistic principles of how SUMO gets conjugated to its substrate. We focus on the interplay of the E1, E2 and E3 enzymes and discuss how specificity could be achieved given the limited number of conjugating enzymes and the thousands of substrates.

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“…For example, the expression of Ubc9 is regulated by miRNA-30a in human subcutaneous adipocytes [34]. miR-30a reduces IRF4 expression through the specific binding with the 3′ UTR, thus suppressing theTh17 differentiation and preventing the full development of autoimmune encephalomyelitis [35].…”

Section: Discussionmentioning

confidence: 99%

miR-30a as Potential Therapeutic by Targeting TET1 through Regulation of the Hydroxymethlation of Drp-1 Promoter in IPF

Zhang¹,

Liu²,

Liu³

et al. 2017

Preprint

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(X.S.) † These authors contributed equally to this work.Abstract：Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous.Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein.Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

show abstract

Mitochondrial Activity in Human White Adipocytes Is Regulated by the Ubiquitin Carrier Protein 9/microRNA-30a Axis

Cited by 31 publications

References 48 publications

miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis

miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis

SUMO conjugation – a mechanistic view

miR-30a as Potential Therapeutic by Targeting TET1 through Regulation of the Hydroxymethlation of Drp-1 Promoter in IPF

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