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Inter3D:Capture of TAD Reorganization Endows Variant Patterns of Gene Transcription

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Genomics, Proteomics & Bioinformatics 2024年第3期22卷 69-84页

作者： Tianyi Ding Shaliu Fu Xiaoyu Zhang Fan Yang Jixing Zhang Haowen Xu Jiaqi Yang Chaoqun Chen Yibing Shi Yiran Bai Wannian Li Xindi Chang Shanjin Wang Chao Zhang Qi Liu He Zhang State Key laboratory of Cardiology and Medical Innovation Center Institute for Regenerative MedicineShanghai East HospitalFrontier Science Research Center for Stem CellsSchool of Life Science and TechnologyTongji UniversityShanghai 200092China Jiangxi Province Key laboratory of Organ Development and epigenetics Clinical Medical Research CenterAffiliated Hospital of Jinggangshan UniversityMedical Department of Jinggangshan UniversityJi'an 343009China School of Life Science Jinggangshan UniversityJi'an 343009China

Topologically associating domain(TAD)reorganization commonly occurs in the cell nucleus and contributes to gene activation and inhibition through the separation or fusion of adjacent ***,functional genes impacted by TAD alteration and the underlying mechanism of TAD reorganization regulating gene transcription remain to be fully ***,we first developed a novel approach termed Inter3D to specifically identify genes regulated by TAD *** study revealed that the segregation of TADs led to the disruption of intrachromosomal looping at the myosin light chain 12B(MYL12B)locus,via the meticulous reorganization of TADs mediating epigenomic landscapes within tumor cells,thereby exhibiting a significant correlation with the down-regulation of its transcriptional ***,the fusion of TADs facilitated intrachromosomal interactions,suggesting a potential association with the activation of cytochrome P450 family 27 subfamily B member 1(CYP27B1).Our study provides comprehensive insight into the capture of TAD rearrangement-mediated gene loci and moves toward understanding the functional role of TAD reorganization in gene *** Inter3D pipeline developed in this study is freely available at https://***/bm2-lab/inter3D and https://***/biocode/tool/BT7399.

关键词： Topologically associating domain Inter3D Chromosomal loop Gene transcription cancer

Author Correction:Enhanced CD19 activity in B cells contributes to immunodeficiency in mice deficient in the ICF syndrome gene Zbtb24

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Cellular & Molecular Immunology 2024年第1期21卷 100-100页

作者： Zhengzhou Ying Swanand Hardikar Joshua B.Plummer Tewfik Hamidi Bin Liu Yueping Chen Jianjun Shen Yunxiang Mu Kevin M.McBride Taiping Chen Department of epigenetics and Molecular Carcinogenesis The University of Texas MD Anderson Cancer Center Houston TX 77030 USA Program in Genetics and epigenetics The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston TX 77030 USA

In the sentence beginning‘To trace cell proliferation,FO and MZ B cells’and the sentence beginning‘For cell activation,naïve B cells or CH12F3 cells’in this article,the[10 ng/ml]‘F(ab’)_(2)fragment goat anti-mouse IgM’should have read‘10μg/ml F(ab’)_(2)fragment goat anti-mouse IgM’.The original article has been corrected.

关键词： immunodeficiency CD19 deficient

NAD+associated genes as potential biomarkers for predicting the prognosis of gastric cancer

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Oncology Research 2024年第2期32卷 283-296页

作者： XIANGDONG SUN HUIJUAN WEN FAZHAN LI IHTISHAM BUKHARI FEIFEI REN XIA XUE PENGYUAN ZHENG YANG MI Henan Key laboratory for Helicobacter Pylori&Microbiota and GI cancer Marshall Medical Research CenterThe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Gastroenterology The Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Nicotinamide adenine dinucleotide(NAD+)plays an essential role in cellular metabolism,mitochondrial homeostasis,inflammation,and ***,the role of NAD+-regulated genes,including coding and long non-coding genes in cancer development is poorly *** constructed a prediction model based on the expression level of NAD+metabolism-related genes(NMRGs).Furthermore,we validated the expression of NMRGs in gastric cancer(GC)tissues and cell lines;additionally,β-nicotinamide mononucleotide(NMN),a precursor of NAD+,was used to treat the GC cell lines to analyze its effects on the expression level of NMRGs lncRNAs and cellular proliferation,cell cycle,apoptosis,and senescence-associated secretory phenotype(SASP).A total of 13 NMRGs-related lncRNAs were selected to construct prognostic risk signatures,and patients with high-risk scores had a poor *** immune checkpoint genes were upregulated in the high-risk *** addition,cell cycle,epigenetics,and senescence were significantly downregulated in the high-risk ***,we found that the levels of immune cell infiltration,including CD8 T cells,CD4 naïve T cells,CD4 memory-activated T cells,B memory cells,and naïve B cells,were significantly associated with risk ***,the treatment of NMN showed increased proliferation of AGS and MKN45 *** addition,the expression of SASP factors(IL6,IL8,IL10,TGF-β,and TNF-α)was significantly decreased after NMN *** conclude that the lncRNAs associated with NAD+metabolism can potentially be used as biomarkers for predicting clinical outcomes of GC patients.

关键词： NAD+ LncRNAs cancer Cell infiltration Prognosis Tumor microenvironment

An overview of multiomics:a powerful tool applied in cancer molecular subtyping for cancer therapy

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Malignancy Spectrum 2024年第1期1卷 15-29页

作者： Yazhu Zou Zitong Zhao Yongmei Song State Key laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

During the process of carcinogenesis and tumor progression,various molecular alternations occur in different omics *** recent years,multiomics approaches including genomics,epigenetics,transcriptomics,proteomics,metabolomics,single-cell omics,and spatial omics have been applied in mapping diverse omics profiles of *** development of high-throughput technologies such as sequencing and mass spectrometry has revealed different omics levels of tumor cells or tissues *** focusing on a single omics level results in a lack of accuracy,joining multiple omics approaches together undoubtedly benefits accurate molecular subtyping and precision medicine for cancer *** the deepening of tumor research in recent years,taking pathological classification as the only criterion of diagnosis and predicting prognosis and treatment response is found to be not accurate ***,identifying precise molecular subtypes by exploring the molecular alternations during tumor occurrence and development is of vital *** review provides an overview of the advanced technologies and recent progress in multiomics applied in cancer molecular subtyping and detailedly explains the application of multiomics in identifying cancer driver genes and metastasis-related genes,exploring tumor microenvironment,and selecting liquid biopsy biomarkers and potential therapeutic targets.

关键词： multiomics cancer molecular subtyping cancer therapy single-cell omics spatial omics

epigenetics(-omics) Takes Center Stage

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Journal of Genetics and Genomics 2013年第7期40卷 323-324页

作者： Jingde Zhu cancer epigenetics laboratory Anhui Cancer Hospital107Huanhudonglu cancer epigenetics laboratory Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong UniversityLN 2200/25Xietu Road

epigenetics concerns non-DNA sequence dependent mechanisms through which cross-mitosis （and meiosis） transmission of committed gene expression pattern in high eukaryotes is achieved. The fact that cells with identical genome can have plentiful phenotypic choices suggests a decisive role of epigenetic regulation in selective gene expression and therefore the biological activities at a cell type-specific manner in multi-cellular organisms. In addition to covalent chemical modifications of DNA and the core histones,

关键词： SLC epigenetics Takes Center Stage omics

Metabolic recoding of epigenetics in cancer

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cancer Communications 2018年第1期38卷 272-279页

作者： Yi-Ping Wang Qun-Ying Lei cancer Institute Fudan University Cancer Hospital and Cancer Metabolism LaboratoryInstitutes of Biomedical SciencesFudan UniversityShanghai 200032P.R.China

Dysregulation of metabolism allows tumor cells to generate needed building blocks as well as to modulate epigenetic marks to support cancer initiation and ***-induced metabolic changes alter the epigenetic landscape,especially modifications on histones and DNA,thereby promoting malignant transformation,adaptation to inadequate nutrition,and *** advances in cancer metabolism shed light on how aberrations in metabolites and metabolic enzymes modify epigenetic *** metabolism-induced recoding of epigenetics in cancer depends strongly on nutrient availability for tumor *** this review,we focus on metabolic remodeling of epigenetics in cancer and examine potential mechanisms by which cancer cells integrate nutritional inputs into epigenetic modification.

关键词： cancer metabolism epigenetics Metabolites Histone modification DNA methylation cancer microenvironment Nutrient availability

Topoisomerase I in Human Disease Pathogenesis and Treatments

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Genomics, Proteomics & Bioinformatics 2016年第3期14卷 166-171页

作者： Min Li Yilun Liu Department of cancer Genetics and epigenetics Beckman Research Institute

Mammalian topoisomerase 1（TOP1） is an essential enzyme for normal ***1 relaxes supercoiled DNA to remove helical constraints that can otherwise hinder DNA replication and transcription and thus block cell ***,this exact activity can covalently trap TOP1 on the DNA that could lead to cell death or mutagenesis,a precursor for *** is therefore important for cells to find a proper balance between the utilization of the TOP1 catalytic activity to maintain DNA topology and the risk of accumulating the toxic DNA damages due to TOP1 trapping that prevents normal cell *** an apparent contradiction to the negative attribute of the TOP1 activity to genome stability,the detrimental effect of the TOP1-induced DNA lesions on cell survival has made this enzyme a prime target for cancer therapies to kill fast-growing cancer *** addition,cumulative evidence supports a direct role of TOP1 in promoting transcriptional progression independent of its topoisomerase *** involvement of TOP1 in transcriptional regulation has recently become a focus in developing potential new treatments for a subtype of autism spectrum ***,the impact of TOP1 on human health is *** this review,we will summarize our current understandings on how TOP1 contributes to human diseases and how its activity is targeted for disease treatments.

关键词： Topoisomerase 1 cancer Autism Scleroderma DNA replication Transcription

TP53-specific mutations serve as a potential biomarker for homologous recombination deficiency in breast cancer:a clinical next-generation sequencing study

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Precision Clinical Medicine 2024年第2期7卷 122-131页

作者： Yongsheng Huang Shuwei Ren Linxiaoxiao Ding Yuanling jiang Jiahuan Luo Jinghua Huang Xinke Yin Jianli Zhao Sha Fu Jianwei Liao Cellular&Molecular Diagnostics Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangdong Provincial Key laboratory of Malignant Tumor epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Clinical laboratory The Sixth Affliated HospitalSun Yat-sen UniversityGuangzhou 510655China Breast Tumor Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangzhou Regenerative Medicine and Health Guangdong LaboratorySun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

Background:TP53 mutations and homologous recombination deficiency(HRD)occur frequently in breast ***,the characteristics of TP53 pathogenic mutations in breast cancer patients with/without HRD are not ***:Clinical next-generation sequencing(NGS)of both tumor and paired blood DNA from 119 breast cancer patients(BRCA-119 cohort)was performed with a 520-gene ***,tumor mutation burden(TMB),and genomic HRD scores were assessed from NGS *** data from 47 breast cancer patients in the HRD test cohort were analyzed for further ***:All TP53 pathogenic mutations in patients had somatic origin,which was associated with the protein expression of estrogen receptor and progestogen *** to patients without TP53 pathologic mutations,patients with TP53 pathologic mutations had higher levels of HRD scores and different genomic *** frequency of TP53 pathologic mutation was higher in the HRDhigh group(HRD score≥42)relative to that in the HRD-low group(HRD scorecancer patients with an area under the curve(AUC)of ***53-specific mutations,namely HRD-low mutation,HRD-high mutation,and HRD common mutation,predicted the HRD status of breast cancer patients with AUC values of 0.32,0.72,and 0.58,***,TP53 HRD-high mutation and HRD common mutation combinations showed the highest AUC values(0.80)in predicting HRD ***:TP53-specific mutation combinations predict the HRD status of patients,indicating that TP53 pathogenic mutations could serve as a potential biomarker for poly-ADP-ribose polymerase(PARP)inhibitors in breast cancer patients.

关键词： next-generation sequencing homologous recombination deficiency TP53 breast cancer

Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2119-2136页

作者： Li Peng Yanyi Jiang Hengxing Chen Yongqiang Wang Qiusheng Lan Shuiqin Chen Zhanwang Huang Jingyuan Zhang Duanqing Tian Yuntan Qiu Diankui Cai Jiangyun Peng Daning Lu Xiaoqing Yuan Xianzhu Yang Dong Yin Guangdong Provincial Key laboratory of Malignant Tumor epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Medical Research Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Hefei Institutes of Physical Science Chinese Academy of SciencesHefei 230031China Department of Gastrointestinal Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Department of Hepatobiliary Surgery Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China

Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug ***,it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors(TFs)except for the nuclear receptor family of *** is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma(GEA)or the therapeutic effects of targeting TF and transcription cofactor *** this study,we found that ETS homologous factor(EHF)expression is promoted by a core transcriptional regulatory circuitry(CRC),specifically ELF3-KLF5-GATA6,and interference with its expression suppressed the malignant biological behavior of GEA ***,we identified Ajuba LIM protein(AJUBA)as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in ***,we identified KRAS signaling as a common pathway downstream of EHF and ***,dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in *** conclusion,EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS *** of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy.

关键词： EHF AJUBA KRAS pathway Enhancer Core transcriptional regulatory circuitry Gastroesophageal adenocarcinoma Gastric adenocarcinoma Esophageal adenocarcinoma Transcription factor Coactivator Lipid nanoparticles