Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were establi...Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.展开更多
Esophageal cancer(EC)has a high incidence and mortality rate and is emerging as one of the most common health problems globally.Owing to the lack of sensitive detection methods,uncontrollable rapid metastasis,and perv...Esophageal cancer(EC)has a high incidence and mortality rate and is emerging as one of the most common health problems globally.Owing to the lack of sensitive detection methods,uncontrollable rapid metastasis,and pervasive treatment resistance,EC is often diagnosed in advanced stages and is susceptible to local recurrence.Exosomes are important components of intercellular communication and the exosome-mediated crosstalk between the cancer and surrounding cells within the tumor microenvironment plays a crucial role in the metastasis,progression,and therapeutic resistance of EC.Considering the critical role of exosomes in tumor pathogenesis,this review focused on elucidating the impact of exosomes on EC metastasis and therapeutic resistance.Here,we summarized the relevant signaling pathways involved in these processes.In addition,we discussed the potential clinical applications of exosomes for the early diagnosis,prognosis,and treatment of EC.展开更多
基金supported by the National Natural Science Foundation of China(81971875,82300661)Natural Science Foundation of Anhui province(2308085QH246)+3 种基金Natural Science Foundation of the Anhui Higher Education Institutions(KJ2021A0205)Basic and Clinical Cooperative Research Program of Anhui Medical University(2019xkjT002,2019xkjT022,2022xkjT013)Talent Training Program,School of Basic Medical Sciences,Anhui Medical University(2022YPJH102)National College Students Innovation and Entrepreneurship Training Program of China(202210366024)。
文摘Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.
基金Supported by the Natural Science Foundation of China,No.82003048 and No.82203284Joint Project of Natural Science Foundation of China,No.U22A2038+2 种基金Anhui Provincial Natural Science Foundation,No.1908085QC131 and No.2008085QH377Research Improvement Program of Anhui Medical University,No.2021xkjT002and Undergraduate Innovation and Entrepreneurship Training Program of Anhui Medical University,No.S202210366044.
文摘Esophageal cancer(EC)has a high incidence and mortality rate and is emerging as one of the most common health problems globally.Owing to the lack of sensitive detection methods,uncontrollable rapid metastasis,and pervasive treatment resistance,EC is often diagnosed in advanced stages and is susceptible to local recurrence.Exosomes are important components of intercellular communication and the exosome-mediated crosstalk between the cancer and surrounding cells within the tumor microenvironment plays a crucial role in the metastasis,progression,and therapeutic resistance of EC.Considering the critical role of exosomes in tumor pathogenesis,this review focused on elucidating the impact of exosomes on EC metastasis and therapeutic resistance.Here,we summarized the relevant signaling pathways involved in these processes.In addition,we discussed the potential clinical applications of exosomes for the early diagnosis,prognosis,and treatment of EC.
