Although aberrant DNA methylation changes are significantly associated with the pathogenesis of many diseases, little is known about the molecular mechanisms underlying interactions between DNA methylation and gene expression in metabolic syndrome (MetS). The aim of this study was to identify biomarkers and molecular mechanisms regulated by DNA methylation in MetS. We profiled genome-wide DNA methylation using the Infinium MethylationEPIC BeadChIP and characterized the transcriptome by RNA sequencing in our study population comprised of subjects with MetS (n = 11) and controls (n = 9). In total, 13,707 significantly differentially methylated probes (DMPs) were identified in subjects with MetS, most in the promoter and coding regions. Among them, 47 DMPs were significantly correlated with the expression of 36 corresponding genes, which were enriched in ‘insulin resistance’, ‘insulin signaling pathway’, and the ‘apelin signaling pathway’. Among these MetSassociated genes, validation of the most discriminating gene via ROC curve analysis, GFPT2, showed significant hypermethylation/downregulated expression in subjects with MetS compared to that in normal controls via bisulfite amplicon sequencing (BSAS) and quantitative real-time PCR (qRT-PCR). Our findings demonstrated altered DNA methylation in subjects with MetS, suggesting that GFPT2 hypermethylation might be a promising epigenetic biomarker and emphasizing the role of aberrant GFPT2 expression in MetS pathogenesis.
Genes&Diseases
语种：英文 出版周期：双月刊
P-ISSN：2352-3042
主管单位：重庆市教育委员会主办单位：重庆医科大学
Genes and Diseases是本由重庆医科大学于2014年创办的双月刊，也是国内第一本分子医学与转化医学相结合的全英文综合期刊，并入选“中国科技期刊卓越行动计划”高起点新刊项目。
目录
过刊浏览
RAPID COMMUNICATION
快讯2022-01-11
Su-Jin Baek，Hyo-Jeong Ban，Sang-Min Park，Soo Yeon Kim，Siwoo Lee，Hee-Jeong Jin
REVIEW ARTICLE
综述2022-02-22
Abhijit Das，Barshana Bhattacharya，Souvik Roy
Cancer is one of those leading diseases worldwide, which takes millions of lives every year. Researchers are continuously looking for specific approaches to eradicate the deadly disease, ensuring minimal adverse effects along with more therapeutic significance. Targeting of different aberrantly regulated signaling pathways, involved in cancer, is surely one of the revolutionary chemotherapeutic approach. In this instance, GSK3 and PI3K signaling cascades are considered as important role player for both the oncogenic activation and inactivation which further leads to cancer proliferation and metastasis. In this review, we have discussed the potential role of GSK3 and PI3K signaling in cancer, and we further established the crosstalk between PI3K and GSK3 signaling, through showcasing their cross activation, cross inhibition and convergence pathways in association with cancer. We also exhibited the effect of GSK3 on the efficacy of PI3K inhibitors to overcome the drug resistance and preventing the cell proliferation, metastasis in a combinatorial way with GSK3 inhibitors for a better treatment strategy in clinical settings.
关键词：Cancer；Chemotherapy；Drug resistance；GSK3；PI3K；
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