Upregulation of lncRNA MEG3 promotes hepatic insulin resistance via increasing FoxO1 expression

Zhu, Xiang; Wu, Yuanyuan; Zhou, Jian; Kang, Dongmei

doi:10.1016/j.bbrc.2015.11.048

Cited by 111 publications

(85 citation statements)

References 33 publications

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“…In fact, in high-fat diet-fed and ob/ob mice, upregulation of MEG3 enhances hepatic insulin resistance by increasing the expression of FoxO1. 57 Interestingly, TET-mediated DNA hypomethylation might be important in the so-called "metabolic memory," which is responsible to mediate the negative effects of hyperglycemia on diabetes complications, even after an acceptable glycemic control is pharmacologically re-established in diabetic patients. 58 More importantly, since the activation of TET enzymes depends upon the activity of the poly (ADP-ribose) polymerase (PARP) enzyme, PARP inhibition in such patients is now a novel candidate therapeutic possibility to halt, or even revert, the progression of diabetic complications.…”

Section: B-cell Development and Functionmentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling b-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on b-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

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Section: B-cell Development and Functionmentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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“…LncRNAs participate in physiological processes of cell-type determination and tissue homeostasis, and it has been proved that LINC00963 was involved in the prostate cancer transition from androgen-dependent to androgen-independent and metastasis via the epidermal growth factor receptor (EGFR) signaling pathway [9]. Moreover, a previous study has demonstrated that overexpression of lncRNA MEG3 promotes hepatic insulin resistance by upregulating forkhead box O (FoxO) 1 expression [10]. As a conserved subfamily of the forkhead transcription factors in evolution, FoxO transcription factors are characterized by the forkhead DNA-binding domain [11].…”

Section: Introductionmentioning

confidence: 99%

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

Chen

Zhang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chronic renal failure (CRF) is usually associated with chronic diseases such as congestive heart failure and diabetes mellitus, the prevalence of which is increased with age. This study is designed to investigate the role of long intergenic non-coding RNA (lincRNA) LINC00963 in renal interstitial fibrosis (RIF) and oxidative stress (OS) of CRF via the forkhead box O (FoxO) signaling pathway. Methods: Microarray data and annotated probe files related to CRF were downloaded by retrieving Gene Expression Omnibus (GEO) database to screen differentially expressed lncRNA. Multi Experiment Matrix (MEM) website and dual-luciferase reporter gene assay were used to predict and verify the target gene of LINC00963, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify the major signaling pathways involved. A total of 60 Wistar male rats were randomly selected and divided into the sham (n = 10) and model (n = 50) groups. Five rats in the sham group and thirty rats in the model group were sub-categorized into the control, blank, negative control (NC), LINC00963 vector, si-LINC00963, si-FoxO3, and si-LINC00963 + si-FoxO3 groups (n = 5). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were performed to evaluate the expressions of LINC00963, FoxO3a, TGF-β1, FN, GSH-PX, Bax, and Bcl-2. Measurement of changes in OS indexes including BUN, MDA, GSH-Px, SOD, and Na⁺-K⁺-ATP were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of inflammatory factors including TNF-α, IL-6, ICAM-1 and FN. TUNEL staining was performed to evaluate cell apoptosis. Results: LINC00963 was highly expressed in CRF rats and FoxO3 was predicted and then verified as a target gene of LINC00963. FoxO3 gene participated in the FOXO signaling pathway. Compared with the blank and NC groups, there were significantly decreased expressions of LINC00963, TGF-β1, FN, and Bax in the si-LINC00963 group, while increased expressions of GSH-PX, FoxO3a, and Bcl-2. The vitality values of BUN and MDA in the si-LINC00963 group declined, while enzymatic activities of GSH-Px, SOD and Na⁺-K⁺-ATP elevated in comparison to the blank and NC groups. The levels of TNF-α, IL-6, ICAM-1 and FN, and cell apoptosis rate in the si-LINC00963 group decreased in comparison to the blank and NC groups. All the results in the si-LINC00963 group were opposite in the LINC00963 vector and si-FoxO3 groups. Conclusion: Taken together, we conclude that down-regulation of LINC00963 suppresses RIF and OS of CRF by activating the FoxO signaling pathway.

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“…30 Knockdown of MEG3 remarkably abolishes hepatic TG accumulation, up- regulates glycogen content, and promotes glucose tolerance in high-fat diet mice and ob/ob mice. Another study showed that MEG3 was highly expressed in mouse islets and was down- regulated during the pathogenesis of diabetes.…”

Section: Lncrnas In Hepatic Lipid and Glucose Metabolismmentioning

confidence: 95%

“…30,43 Recently, MEG3 was identified as a guide RNA scaffold to recruit PTBP1 to destabilize nuclear receptor Shp mRNA in cholestatic liver injury. 44 Overexpression of MEG3 RNA induced a rapid Shp mRNA degradation and elevation of liver injury enzymes such as ALT and AST in mouse liver, and disrupted bile acids homeostasis.…”

Section: Lncrna In Cholestatic Liver Diseasementioning

confidence: 99%

Long non-coding RNA in liver metabolism and disease: Current status

Zhao

Liangpunsakul

et al. 2017

Liver Research

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Long non-coding RNAs (lncRNAs) are comprised of RNA transcripts exceeding 200 nucleotides in length but lacking identifiable open reading frames (with rare exceptions). Herein, we highlight emerging evidence demonstrating that lncRNAs are critical regulators of liver metabolic function and diseases. We summarize current knowledges about dysregulated lncRNAs and outline the underlying molecular mechanisms by which lncRNAs control hepatic lipid ad glucose metabolism, as well as cholestatic liver disease. lncLSTR, Lnc18q22.2, SRA, HULC, MALAT1, lncLGR, MEG3, and H19, lncHR1, lnc-HC, APOA1-AS, DYNLRB2-2, and LeXis are included in the discussion.

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Upregulation of lncRNA MEG3 promotes hepatic insulin resistance via increasing FoxO1 expression

Cited by 111 publications

References 33 publications

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

Effects of Long Non-Coding RNA LINC00963 on Renal Interstitial Fibrosis and Oxidative Stress of Rats with Chronic Renal Failure via the Foxo Signaling Pathway

Long non-coding RNA in liver metabolism and disease: Current status

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