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Evaluation of biomarkers, genetic mutations, and epigenetic modifications in early diagnosis of pancreatic cancer

World Journal of Gastroenterology 2021年第36期27卷 6093-6109页

作者： Bilal Rah Manzoor Ahmad Banday Gh Rasool Bhat Omar J Shah Humira Jeelani Fizalah Kawoosa Tahira Yousuf Dil Afroze Advanced Centre for Human Genetics Sher-i-Kashmir Institute of Medical SciencesSrinagar 190011Jammu and KashmirIndia Department of Medical Oncology Sher-i-Kashmir Institute of Medical SciencesSrinagar 190011Jammu and KashmirIndia Department of Surgical Gastroenterology Sher-i-Kashmir Institute of Medical SciencesSrinagar 190011Jammu and KashmirIndia Department of Immunology and Molecular Medicine Sher-i-Kashmir Institute of Medical ScienceSrinagar 190011Jammu and KashmirIndia

BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality *** significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognosis,marred by mutations and epigenetic modifications in key genes which contribute to disease *** To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir *** A total of 50 confirmed PC cases were included in the study to evaluate the levels of carbohydrate antigen 19-9(CA 19-9),tissue polypeptide specific antigen(TPS),carcinoembryonic antigen(CEA),vascular endothelial growth factor-A(VEGF-A),and epidermal growth factor receptor(EGFR).Mutational analysis was performed to evaluate the mutations in Kirsten rat sarcoma(KRAS),Breast cancer type 2(BRCA-2),and deleted in pancreatic cancer-4(DPC-4)***,epigenetic modifications(methylation of CpG islands)were performed in the promoter regions of cyclin-dependent kinase inhibitor 2A(p16;CDKN2A),MutL homolog 1(hMLH1),and Ras association domain-containing protein 1(RASSF1A)*** We found significantly elevated levels of biological markers CA 19-9(P≤0.05),TPS(P≤0.05),CEA(P≤0.001),and VEGF(P≤0.001).Molecular genetic analysis revealed that KRAS gene mutation is predominant in codon 12(16 subjects,P≤0.05),and 13(12 subjects,P≤0.05).However,we did not find a mutation in DPC-4(1203G>T)and BRCA-2(617delT)***,epigenetic modification revealed that CpG methylation in 21(P≤0.05)and 4 subjects in the promoter regions of the p16 and hMLH1 gene,*** In conclusion,CA 19-9,TPS,CEA,and VEGF levels were significantly elevated and collectively have potential as diagnostic and prognostic markers in *** data of mutation in the KRAS gene commonly in codon 12 and rare in codon 13 could augment the predisposition towards ***,methylatio

关键词： Pancreatic cancer Genetic mutations epigenetic modifications Biomarkers Risk factors Diagnostics

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RECENT ADVANCES IN THE REGULATION OF CLIMACTERIC FRUIT RIPENING:HORMONE,TRANSCRIPTION FACTOR AND epigenetic modifications

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Frontiers of Agricultural Science and Engineering 2021年第2期8卷 314-334页

作者： Yinglin JI Mingyang XU Aide WANG Key Laboratory of Fruit Postharvest Biology of Liaoning Province College of HorticultureShenyang Agricultural UniversityShenyang 110866China.

Fruit ripening is a complex developmental process made up of genetically programmed physiological and biochemical *** culminates in desirable changes in the structural and textural properties and is governed by a complex regulatory *** is known about ethylene,one of the most important metabolites promoting the ripening of climacteric ***,the dynamic interplay between phytohormones also plays an important *** regulatory factors such as transcription factors(TFs)and epigenetic modifications also play vital role in the regulation of climacteric fruit ***,we review and evaluate the complex regulatory network comprising interactions between hormones and the action of TFs and epigenetic modifications during climacteric fruit ripening.

关键词： climacteric fruit ripening phytohormones TFs epigenetic modifications

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Connections between metabolism and epigenetic modifications in cancer

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Medical Review 2021年第2期1卷 199-221页

作者： Guangchao Wang Jingdong J.Han Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology(CQB)Peking University5 Yiheyuan RdHaidian DistrictBeijing 100871China

How cells sense and respond to environmental changes is still a key *** has been identified that cellular metabolism is an important modifier of various epigenetic modifications,such as DNA methylation,histone methylation and acetylation and RNA N6-methyladenosine(m6A)*** closely links the environmental nutrient availability to the maintenance of chromatin structure and gene expression,and is crucial to regulate cellular homeostasis,cell growth and *** metabolic reprogramming and epigenetic alterations are widely observed,and facilitate cancer development and *** cancer cells,oncogenic signaling-driven metabolic reprogramming modifies the epigenetic landscape via changes in the keymetabolite *** this review,we briefly summarized the current evidence that the abundance of key metabolites,such as S-adenosyl methionine(SAM),acetyl-CoA,α-ketoglutarate(α-KG),2-hydroxyglutarate(2-HG),uridine diphospho-N-acetylglucosamine(UDP-GlcNAc)and lactate,affected by metabolic reprogramming plays an important role in dynamically regulating epigenetic modifications in *** improved understanding of the roles of metabolic reprogramming in epigenetic regulation can contribute to uncover the underlying mechanisms of metabolic reprogramming in cancer development and identify the potential targets for cancer therapies.

关键词： cancer metabolic reprogramming DNA methylation epigenetic modifications histone acetylation histone methylation RNA m6A.

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Redox and metabolic regulation of epigenetic modifications:an emerging toxic action mechanism

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Toxicology Advances 2023年第3期5卷 1-12页

作者： Wan-Qian Guo Wu-Sheng Xiao Wei-Dong Hao Department of Toxicology School of Public HealthPeking UniversityBeijing 100191China Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety Beijing 100191China

epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and *** activities of epigenetic modifying enzymes depend on many co-substrates and cofactors,such as 2-oxoglutarate(2-OG),iron,S-adenosylmethionine(SAM),nicotinamide adenine dinucleotide(NAD+),flavin adenine dinucleotide(FAD),and *** factors are inter-connecting molecules that integrate cellular nutrient metabolism and redox homeostasis,two key regulators of cell proliferation,cell survival,and cell *** of such delicate regulatory network has been implicated in many pathological conditions and also been increasingly recognized as an emerging mechanism responsible for environmental pollutant-induced adverse *** this review,we first summarize DNA and histone modifying enzymes and their essential factors,then discuss the metabolic sources and the redox regulatory roles of these enzymatic factors,and finally elaborate the mechanisms of how targeting such factors by environmental pollutants influences epigenetic regulation and perturbs cellular functions.

关键词： epigenetic modifications redox state cellular metabolism

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Histone modifications and alcohol-induced liver disease:Are altered nutrients the missing link?

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World Journal of Gastroenterology 2011年第20期17卷 2465-2472页

作者： Akshata Moghe Swati Joshi-Barve Smita Ghare Leila Gobejishvili Irina Kirpich Craig J McClain Shirish Barve University of Louisville Alcohol Research Center Department of Pharmacology and Toxicology University of Louisville Department of Internal Medicine Division of GastroenterologyHepatology and NutritionUniversity of Louisville Robley Rex Veterans Affairs Medical Center

Alcoholism is a major health problem in the United States and worldwide,and alcohol remains the single most significant cause of liver-related diseases and *** is known to influence nutritional status at many levels including nutrient intake,absorption,utilization,and excretion,and can lead to many nutritional disturbances and *** can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease(ALD).There is growing interest regarding epigenetic changes,including histone modifications that regulate gene expression during disease ***,modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation,and control gene *** review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to *** review is focused on four critical metabolites,namely,acetate,S-adenosylmethionine,nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.

关键词： Alcohol Liver disease Nutrients Metabolism Histone epigenetic modifications S-adenosylmethionine Acetate Zinc NAD

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Contribution of epigenetics in diabetic retinopathy

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Science China(Life Sciences) 2015年第6期58卷 556-563页

作者： KOWLURU Renu A. MISHRA Manish Kresge Eye Institute Wayne State University

Diabetes has become the epidemic of the 21 st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite of cutting edge research in the field, how retina and its vasculature are damaged by the diabetic milieu remains ambiguous. The environmental factors, life style or disease process can also bring in modifications in the DNA, and these epigenetic modifications either silence or activate a gene without altering the DNA sequence. Diabetic environment up- or downregulates a number of genes in the retina, and emerging research has shown that it also facilitates epigenetic modifications. In the pathogenesis of diabetic retinopathy, the genes associated with important enzymes(e.g., mitochondrial superoxide dismutase, matrix metalloproteinase-9 and thioredoxin interacting protein) and transcriptional factors are epigenetically modified, the enzymes responsible for these epigenetic modifications are either activated or inhibited, and the levels of micro RNAs are altered. With epigenetic modifications taking an important place in diabetic retinopathy, it is now becoming critical to evaluate these modifications, and understand their impact on this slow progressing blinding disease.

关键词： diabetic retinopathy epigenetic modifications histone acetylation histone methylation miRNA

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Metabolic memory: mechanisms and implications for diabetic vasculopathies

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Science China(Life Sciences) 2014年第8期57卷 845-851页

作者： ZHANG ErLi WU YongJian State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical College

In the past decades,a persistent progression of diabetic vascular complications despite reversal of hyperglycemia has been observed in both experimental and clinical *** durable effect of prior hyperglycemia on the initiation and progression of diabetic vasculopathies was defined as"metabolic memory".Subsequently,enhanced glycation of cellular proteins and lipids,sustained oxidative stress,and prolonged inflammation were demonstrated to mediate this ***,emerging evidence strongly suggests that epigenetic modifications may account for the molecular and phenotypic changes associated with hyperglycemic *** this review,we presented an overview on the discovery of metabolic memory,the recent progress in its molecular mechanisms,and the future implications related to its fundamental research and clinical application.

关键词： diabetic vascular complications metabolic memory oxidative stress inflammation epigenetic modifications

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Priming of antiherbivore defensive responses in plants

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Insect Science 2013年第3期20卷 273-285页

作者： Jinwon Kim Gary W. Felton Department of Entomology Pennsylvania State University University Park PA 16802 United States

Abstract Defense priming is defined as increased readiness of defense induction. A growing body of literature indicates that plants （or intact parts of a plant） are primed in anticipation of impending environmental stresses, both biotic and abiotic, and upon the following stimulus, induce defenses more quickly and strongly. For instance, some plants previously exposed to herbivore-inducible plant volatiles （HIPVs） from neighboring plants under herbivore attack show faster or stronger defense activation and enhanced insect resistance when challenged with secondary insect feeding. Research on priming of antiherbivore defense has been limited to the HIPV-mediated mechanism until recently, but significant advances were made in the past three years, including non-HIPV-mediated defense priming, epigenetic modifications as the molecular mechanism of priming, and others. It is timely to consider the advances in research on defense priming in the plant- insect interactions.

关键词： defense priming epigenetic modifications plant-insect interactions

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Centromere repositioning and shifts in wheat evolution

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Plant Communications 2023年第4期4卷 117-131页

作者： Jing Zhao Yilin Xie Chuizheng Kong Zefu Lu Haiyan Jia Zhengqiang Ma Yijing Zhang Dangqun Cui Zhengang Ru Yuquan Wang Rudi Appels Jizeng Jia Xueyong Zhang Key Laboratory of Crop Gene Resources and Germplasm Enhancement Ministry of Agriculture and Rural Affairs/Institute of Crop ScienceChinese Academy of Agricultural SciencesBeijing 100081China National Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China Nanjing Agricultural University Nanjing 210095JiangsuChina Agronomy College/National Key Laboratory of Wheat and Maize Crop Science/Collaborative Innovation Center of Henan Grain Crops Henan Agricultural UniversityZhengzhou 450046China Henan Institute of Science and Technology Xinxiang 453003China Agriculture Victoria Research Department of Economic DevelopmentJobsTransport and ResourcesAgriBioBundooraVIC 3083Australia University of the Chinese Academy of Sciences Beijing 100049China

The centromere is the region of a chromosome that directs its separation and plays an important role in cell division and reproduction of *** the dynamics of centromeres is an alternative strategy for exploring the evolution of ***,we comprehensively analyzed centromeres from the de novoassembled common wheat cultivar Aikang58(AK58),Chinese Spring(CS),and all sequenced diploid and tetraploid ancestors by chromatin immunoprecipitation sequencing,whole-genome bisulfite sequencing,RNA sequencing,assay for transposase-accessible chromatin using sequencing,and comparative *** found that centromere-associated sequences were concentrated during tetraploidization and *** repeats of wheat(CRWs)have undergone expansion during wheat evolution,with strong interweaving between the A and B subgenomes post *** found that CENH3 prefers to bind with younger CRWs,as directly supported by immunocolocalization on two chromosomes(1A and 2A)of wild emmer wheat with dicentromeric regions,only one of which bound with *** a comparison of AK58 with CS,obvious centromere repositioning was detected on chromosomes 1B,3D,and *** active centromeres showed a unique combination of lower CG but higher CHH and CHG methylation *** also found that centromeric chromatin was more open than pericentromeric chromatin,with higher levels of gene expression but lower gene *** introgression between tetraploid and hexaploid wheat also had a strong influence on centromere position on the same *** study also showed that active wheat centromeres were genetically and epigenetically determined.

关键词： wheat evolution centromere repositioning epigenetic modifications

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R-loop:The new genome regulatory element in plants

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Journal of Integrative Plant Biology 2022年第12期64卷 2275-2289页

作者： Jincong Zhou Weifeng Zhang Qianwen Sun Center for Plant Biology School of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua Peking Center for Life Sciences Bejing 100084China

An R-loop is a three-stranded chromatin structure that consists of a displaced single strand of DNA and an RNA:DNA hybrid duplex,which was thought to be a rare by-product of ***,recent genome-wide data have shown that R-loops are widespread and pervasive in a variety of genomes,and a growing body of experimental evidence indicates that R-loops have both beneficial and harmful effects on an *** maximize benefit and avoid harm,organisms have evolved several means by which they tightly regulate R-loop ***,we summarize our current understanding of the biogenesis and effects of R-loops,the mechanisms that regulate them,and methods of R-loop profiling,reviewing recent research advances on R-loops in ***,we provide perspectives on future research directions for R-loop biology in plants,which might lead to a more comprehensive understanding of R-loop functions in plant genome regulation and contribute to future agricultural improvements.

关键词： chromatin architecture epigenetic modifications genome stability replication R-loop transcription

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