TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal muscle

Mudry, Jonathan M.; Massart, Julie; Szekeres, Ferenc; Krook, Anna

doi:10.1530/joe-14-0474

Cited by 23 publications

(19 citation statements)

References 38 publications

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“…High TWIST protein expression has been shown in a positive correlation with poor prognosis in many cancers, including HNSCC [ 7 , 26 , 27 , 35 – 37 ]. TWIST1 and TWIST2 share more than 90% sequence homology and structural similarity, and they have similar biochemical properties in vitro , and overlap in localization and expression pattern [ 14 , 15 , 38 ]. Thus, it was thought that overexpression of TWIST1 and/or TWIST2 was similarly correlated to poor prognosis in HNSCCs [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

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Smoking and gender modify the effect of TWIST on patient survival in head and neck squamous carcinoma

2017

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PurposeTWIST is a critical factor for predicting prognosis in several human cancers. Here, we study the prognostic significance of TWIST1 and TWIST2 in Head and Neck squamous cell carcinoma (HNSCC) as well as interactions of TWISTs with both gender and smoking in patient survival.Methodsupper quartile normalized RNA-seq V2 RSEM values of TWIST1 and TWIST2 expressions were retrieved from a TCGA HNSCC dataset. Kaplan-Meier survival curves were used to assess the associations of TWIST1 and TWIST2 with patient survival, and multivariate Cox proportional hazards regression models were used to estimate the hazards ratios (HRs) and their 95% confidence intervals (CIs).ResultsSurvival analyses showed that high TWIST1 expression was associated with a poor overall survival at a borderline significance level, while a superior but not statistically significant overall survival was observed in high TWIST2 expression. The multivariate Cox proportional hazards regression model showed a significantly elevated risk of death (HR=1.37, p = 0.038) in patients with high TWIST1 compared to low TWIST1, and a borderline significantly decreased risk of death (HR = 0.74, p = 0.055) in patients with high TWIST2 compared to low TWIST2. Further stratification analyses showed that increased risks of death were found significantly in male and borderline significantly in smoker patients with high TWIST1 compared to low one, and a significantly decreased risk of death in non-smoker patients with high TWIST2 compared to low one.ConclusionsTWIST1 and TWIST2 are differentially associated with HNSCC patient survival. Gender and smoking could modify the effect of TWISTs on the risk of death in HNSCC patients.

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Section: Discussionmentioning

confidence: 99%

“…In mammals, there are two forms of TWIST, TWIST1 and TWIST2. The two isoforms share more than 90% sequence homology and structural similarity, have similar biochemical properties in vitro , and are co-expressed in many cell lines and tissues [ 14 , 15 ]. However, the two isoforms can function differentially in carcinoma metastasis.…”

Section: Introductionmentioning

confidence: 99%

Smoking and gender modify the effect of TWIST on patient survival in head and neck squamous carcinoma

2017

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“…Glucose uptake, glucose incorporation into glycogen, and palmitate oxidation were determined in primary human skeletal muscle cells, as previously described (15,17). Glucose uptake was measured in myotubes incubated in the absence or presence of insulin (120 nmol/L) in glucose-and serumfree DMEM before the addition of 2-[1,2-3 H]deoxy-D-glucose and 10 mmol/L unlabeled 2-deoxy-D-glucose.…”

Section: Primary Human Skeletal Muscle Cell Culturementioning

confidence: 99%

Altered miR-29 Expression in Type 2 Diabetes Influences Glucose and Lipid Metabolism in Skeletal Muscle

et al. 2017

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MicroRNAs have emerged as important regulators of glucose and lipid metabolism in several tissues; however, their role in skeletal muscle remains poorly characterized. We determined the effects of the miR-29 family on glucose metabolism, lipid metabolism, and insulin responsiveness in skeletal muscle. We provide evidence that miR-29a and miR-29c are increased in skeletal muscle from patients with type 2 diabetes and are decreased following endurance training in healthy young men and in rats. In primary human skeletal muscle cells, inhibition and overexpression strategies demonstrate that miR-29a and miR-29c regulate glucose uptake and insulin-stimulated glucose metabolism. We identified that miR-29 overexpression attenuates insulin signaling and expression of insulin receptor substrate 1 and phosphoinositide 3-kinase. Moreover, miR-29 overexpression reduces hexokinase 2 expression and activity. Conversely, overexpression of miR-29 by electroporation of mouse tibialis anterior muscle decreased glucose uptake and glycogen content in vivo, concomitant with decreased abundance of GLUT4. We also provide evidence that fatty acid oxidation is negatively regulated by miR-29 overexpression, potentially through the regulation of peroxisome proliferator-activated receptor γ coactivator-1α expression. Collectively, we reveal that miR-29 acts as an important regulator of insulin-stimulated glucose metabolism and lipid oxidation, with relevance to human physiology and type 2 diabetes.

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“…Among these genes, TWIST2 was consistently observed with hypermethylation in its promoter DMR in IUGR piglets. As TWIST2 functions in regulating immune-metabolic genes (Galván et al 2015 ; Mudry et al 2015 ; Zheng et al 2015 ), its potential down-regulation of transcription due to promoter hypermethylation may hamper intestinal development in IUGR piglets. The other two genes, AIFM1 and MTMR1, were both hypomethylated in the IUGR piglets, implying for potential up-regulation of gene expression.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction

Gong

et al. 2018

Mol Genet Genomics

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Intrauterine growth restriction (IUGR) may elicit a series of postnatal body developmental and metabolic diseases due to their impaired growth and development in the mammalian embryo/fetus during pregnancy. In the present study, we hypothesized that IUGR may lead to abnormally regulated DNA methylation in the intestine, causing intestinal dysfunctions. We applied reduced representation bisulfite sequencing (RRBS) technology to study the jejunum tissues from four newborn IUGR piglets and their normal body weight (NBW) littermates. The results revealed extensively regional DNA methylation changes between IUGR/NBW pairs from different gilts, affecting dozens of genes. Hiseq-based bisulfite sequencing PCR (Hiseq-BSP) was used for validations of 19 genes with epigenetic abnormality, confirming three genes (AIFM1, MTMR1, and TWIST2) in extra samples. Furthermore, integrated analysis of these 19 genes with proteome data indicated that there were three main genes (BCAP31, IRAK1, and AIFM1) interacting with important immunity- or metabolism-related proteins, which could explain the potential intestinal dysfunctions of IUGR piglets. We conclude that IUGR can lead to disparate DNA methylation in the intestine and these changes may affect several important biological processes such as cell apoptosis, cell differentiation, and immunity, which provides more clues linking IUGR and its long-term complications.Electronic supplementary materialThe online version of this article (10.1007/s00438-018-1422-9) contains supplementary material, which is available to authorized users.

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TWIST1 and TWIST2 regulate glycogen storage and inflammatory genes in skeletal muscle

Cited by 23 publications

References 38 publications

Smoking and gender modify the effect of TWIST on patient survival in head and neck squamous carcinoma

Smoking and gender modify the effect of TWIST on patient survival in head and neck squamous carcinoma

Altered miR-29 Expression in Type 2 Diabetes Influences Glucose and Lipid Metabolism in Skeletal Muscle

Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction

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