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The roles and mechanisms of SREBP1 in cancer development and drug response

Genes & Diseases 2024年第4期11卷 258-269页

作者： Ying He Shasha Qi Lu Chen Jinyu Zhu Linda Liang Xudong Chen Hao Zhang Lvjia Zhuo Shujuan Zhao Shuiping Liu Tian Xie School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang 311121China key laboratory of Elemene Class Anti-cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China laboratory of cancer genomics Division of Cellular and Molecular ResearchNational Cancer Centre SingaporeSingapore 169610Singapore

cancer occurrence and development are closely related to increased lipid produc-tion and glucose *** are the basic component of the cell membrane and play a significant role in cancer cell processes such as cell-to-cell recognition,signal transduction,and energy supply,which are vital for cancer cell rapid proliferation,invasion,and *** regulatory element-binding transcription factor 1(SREBP1)is a key transcription factor regulating the expression of genes related to cholesterol biosynthesis,lipid homeostasis,and fatty acid *** addition,SREBP1 and its upstream or downstream target genes are implicated in various metabolic diseases,particularly ***,no review of sREBP1 in cancer biology has yet been ***,we summarized the roles and mechanisms of SREBP1 biological processes in cancer cells,including SREBP1 modification,lipid metabolism and reprogramming,glucose and mitochondrial metabolism,immunity,and tumor microenvi-ronment,epithelial-mesenchymal transition,cell cycle,apoptosis,and ***-ally,we discussed the potential role of SREBP1 in cancer prognosis,drug response such as drug sensitivity to chemotherapy and radiotherapy,and the potential drugs targeting SREBP1 and its corresponding pathway,elucidating the potential clinical application based on SREBP1 and its corresponding signal pathway.

关键词： cancer Drug Lipid metabolism reprogramming Resistance SREBP1

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The Wnt-dependent and Wnt-independent functions of BCL9 in development,tumorigenesis,and immunity:Implications in therapeutic opportunities

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Genes & Diseases 2024年第2期11卷 701-710页

作者： Minjie Wu Heng Dong Chao Xu Mengqing Sun Haojin Gao Fangtian Bu Jianxiang Chen College of Pharmacy and Department of Hepatology Institute of Hepatology and Metabolic DiseasesThe Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhouZhejiang 311121China laboratory of cancer genomics Division of Cellular and Molecular ResearchNational Cancer CentreSingapore 169610Singapore key laboratory of Elemene Class Anti-cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China

B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin ***,increasing evidences indicate that BCL9 also plays multiple Wnt-independent ***,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological ***,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.

关键词： BCL9 Development Immunity Multifaceted functions Therapeutic target Tumorigenesis

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IMAGGS: a radiogenomic framework for identifying multi-way associations in breast cancer subtypes

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Journal of Genetics and genomics 2024年第4期51卷 443-453页

作者： Shuyu Liang Sicheng Xu Shichong Zhou Cai Chang Zhiming Shao Yuanyuan Wang Sheng Chen Yunxia Huang Yi Guo Department of Electronic Engineering School of Information Science and TechnologyFudan UniversityShanghai 200433China The key laboratory of medical Imaging Computing and Computer Assisted intervention(MICCAI)of Shanghai Shanghai 200032China Shanghai key laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200433China Department of Ultrasound Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Department of Breast Surgery Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China

Investigating correlations between radiomic and genomic profiling in breast cancer(BC)molecular subtypes is crucial for understanding disease mechanisms and providing personalized *** present a well-designed radiogenomic framework image–gene–gene set(IMAGGS),which detects multi-way associations in BC subtypes by integrating radiomic and genomic *** dataset consists of 721 patients,each of whom has 12 ultrasound(US)images captured from different angles and gene mutation *** better characterize tumor traits,12 multi-angle US images are fused using two distinct ***,we analyze complex many-to-many associations between phenotypic and genotypic features using a machine learning algorithm,deviating from the prevalent one-to-one relationship pattern observed in previous *** radiomic and genomic features are screened using these *** addition,gene set enrichment analysis is performed to investigate the joint effects of gene sets and delve deeper into the biological functions of BC *** further validate the feasibility of IMAGGS in a glioblastoma multiforme dataset to demonstrate the scalability of IMAGGS across different modalities and *** together,IMAGGS provides a comprehensive characterization for diseases by associating imaging,genes,and gene sets,paving the way for biological interpretation of radiomics and development of targeted therapy.

关键词： IMAGGS Radiogenomic framework "lmage-gene-geneset"associations Molecular subtypes Breast cancer

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Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

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cancer Communications 2024年第2期44卷 287-293页

作者： Kouya Shiraishi Atsushi Takahashi Yukihide Momozawa Yataro Daigo Syuzo Kaneko Takahisa Kawaguchi Hideo Kunitoh Shingo Matsumoto Hidehito Horinouchi Akiteru Goto Takayuki Honda Kimihiro Shimizu Masahiro Torasawa Daisuke Takayanagi Motonobu Saito Akira Saito Yuichiro Ohe Shun-ichi Watanabe Koichi Goto Masahiro Tsuboi Katsuya Tsuchihara Sadaaki Takata Tomomi Aoi Atsushi Takano Masashi Kobayashi Yohei Miyagi Kazumi Tanaka Hiroyuki Suzuki Daichi Maeda Takumi Yamaura Maiko Matsuda Yoko Shimada Takaaki Mizuno Hiromi Sakamoto Teruhiko Yoshida Yasushi Goto Tatsuya Yoshida Taiki Yamaji Makoto Sonobe Shinichi Toyooka Kazue Yoneda Katsuhiro Masago Fumihiro Tanaka Megumi Hara Nobuo Fuse Satoshi S.Nishizuka Noriko Motoi Norie Sawada Yuichiro Nishida Kazuki Kumada Kenji Takeuchi Kozo Tanno Yasushi Yatabe Kuniko Sunami Tomoyuki Hishida Yasunari Miyazaki Hidemi Ito Mitsuhiro Amemiya Hirohiko Totsuka Haruhiko Nakayama Tomoyuki Yokose Kazuyoshi Ishigaki Toshiteru Nagashima Yoichi Ohtaki Kazuhiro Imai Ken Takasawa Yoshihiro Minamiya Kazuma Kobayashi Kenichi Okubo Kenji Wakai Atsushi Shimizu Masayuki Yamamoto Motoki Iwasaki Koichi Matsuda Johji Inazawa Yuichi Shiraishi Hiroyoshi Nishikawa Yoshinori Murakami Michiaki Kubo Fumihiko Matsuda Yoichiro Kamatani Ryuji Hamamoto Keitaro Matsuo Takashi Kohno division of Genome Biology National Cancer Center Research InstituteTokyoJapan Department of Clinical genomics National Cancer Center Research InstituteTokyoJapan laboratory for Statistical Analysis Center for Integrative Medical SciencesRIKENYokohamaJapan Department of Genomic Medicine Research InstituteNational Cerebral and Cardiovascular CenterOsakaJapan laboratory for Genotyping Development Center for Integrative Medical SciencesRIKENYokohamaJapan Center for Antibody and Vaccine Therapy Research HospitalInstitute of Medical ScienceThe University of TokyoTokyoJapan Department of medical Oncology and cancer Center and Center for Advanced Medicine against CancerShiga University of Medical ScienceOtsuJapan division of medical AI Research and Development National Cancer Center Research InstituteTokyoJapan Center for Genomic Medicine Graduate School of MedicineKyoto UniversityKyotoJapan Department of medical Oncology Japanese Red Cross Medical CenterTokyoJapan Department of Thoracic Oncology National Cancer Center Hospital EastJapan Department of Thoracic Oncology National Cancer Center HospitalTokyoJapan Department of Cellular and Organ Pathology Graduate School of MedicineAkita UniversityAkitaJapan Department of Respiratory Medicine Tokyo Medical and Dental UniversityBunkyo-kuTokyoJapan division of General Thoracic Surgery Department of SurgeryShinshu University School of MedicineMatsumotoNaganoJapan Department of General Surgical Science Division of General Thoracic SurgeryGunma University Graduate School of MedicineIntegrative Center of General SurgeryGunma University HospitalGunmaJapan Department of Gastrointestinal Tract Surgery Fukushima Medical University School of MedicineFukushimaJapan StaGen Co. LtdTokyoJapan division of Thoracic Surgery National Cancer Center HospitalTokyoJapan Department of Thoracic Surgery National Cancer Center Hospital EastChibaJapan division of Translational Informatics Exploratory Oncology Research and Clinical Trial Center(EPOC

Dear editor,Lung carcinoma is responsible for the highest fatal-ity rate among cancer-related deaths globally,with lung adenocarcinoma(LADC)emerging as the prevailing sub-type.

关键词： adenocarcinoma lung Lung

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Lack of evidence for germline WWP1 pathogenic variants in gastrointestinal polyposis and other phenotypes suggestive of PTEN-hamartoma-tumor syndrome

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Genes & Diseases 2024年第2期11卷 524-527页

作者： Noemi Gonzalez-Abuin Tirso Pons Teresa Fuster Isabel Quintana Mariona Terradas Gemma Aiza Joan Brunet Gabriel Capellá Heather Hampel Laura Valle Hereditary cancer Program Catalan Institute of OncologyOncobell ProgramIDIBELLHospitalet de LlobregatBarcelona 08908Spain Department of Immunology and Oncology National Center for BiotechnologySpanish National Research Council (CNB-CSIC)Madrid 28049Spain Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Madrid 28029Spain Catalan institute of Oncology IDIBGiGirona 17007Spain division of Clinical cancer genomics Department of Medical Oncology & Therapeutic ResearchCity of Hope National Cancer CenterDuarteCA 91010USA

Germline activating variants in WWP1,which encodes an E3 ubiquitin ligase that antagonizes PTEN tumor suppressive function,have been proposed as an alternative mechanism of PTEN inactivation in PTEN-hamartoma-tumor syndrome(PHTS)-like patients with wildtype PTEN.1 More specifically,heterozygous,potentially activating wwP1 variants were first identified by Lee et al in patients affected with gastrointestinal oligopolyposis,including adenomatous,hyperplastic/serrated,and hamartomatous polyps,and occasionally with colorectal cancer(Table 1).Subsequently,based on the PHTS phenotypic features,wWP1 mutational screening was performed in patients with thyroid nodules,2 or normocephalic autism spectrum disorder(ASD),3 where germline WWP1 variants were also identified(Table S1).

关键词： WWP1 gastrointestinal polyposis

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Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

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Neural Regeneration Research 2024年第5期19卷 1133-1141页

作者： Baicheng Zhao Hang Zhang Ying Liu Gaoyu Zu Yuxiao Zhang Jiayi Hu Shuai Liu Linya You Department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghaiChina Shanghai key laboratory of Brain Functional genomics(Ministry of Education) Affiliated Mental Health Center(ECNU)School of Psychology and Cognitive ScienceEast China Normal UniversityShanghaiChina Shanghai Changning Mental Health Center ShanghaiChina NYU-ECNU institute of Brain and Cognitive Science at NYU Shanghai ShanghaiChina key laboratory of medical Imaging Computing and Computer Assisted intervention of Shanghai ShanghaiChina

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/***1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual *** previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and ***,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory *** test this,we knocked out Brpf1 in forebrain excitatory neurons using *** found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in *** findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

关键词： behavioral test Brpf1 CAMKIIa-Cre intellectual disability miniature excitatory postsynaptic current mRNA-Seq

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Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

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Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang Wenjuan Tang Haitao Niu William Tse Hai-Bin Ruan Helmut Dolznig Thomas Knosel Friedrich Karl-Heinz Madeleine Themanns Jiang Wang Mingquan Song Lee Denson Lukas Kenner Richard Moriggl Yi Zheng Xiaonan Han division of Hematology and Oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA cancer genomics and Epigenomics Program Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA division of Gastroenterology Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Children’s Hospital of Fudan University Shanghai 201102China School of Medicine Jinan UniversityGuangzhouGuangdong 510632China laboratory Animal Science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Department of Integrative Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA institute of medical Genetics Medical University of ViennaVienna 1040Austria institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany institute of Biochemistry II University Hospital JenaJena 07743Germany laboratory Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Department of Pathology University of CincinnatiCincinnatiOH 45221USA Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Department of Pathology Medical University of ViennaVienna 1040Austria Ludwig Boltzmann institute for cancer Research Vienna 1090Austria medical University of Vienna Vienna 1040Austria institute of Animal Breeding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria division of Experimental Hematology CCHMCCincinnatiOH 45229USA

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)*** aberrant CDC42 initiates intestinal inflammation or neoplasia is *** utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and *** specimens were collected to determine the levels of CDC42 in IBD or colorectal ***42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient ***,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC *** studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD *** Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt *** Cdc42 depletion markedly enhanced irra-diation-or chemical-induced *** or inhibition of Cdc42 reduced colonic Lgr5+IESC *** conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Colorectal cancer(CRC) Inflammatory bowel diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Irradiation

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Structure of a histone hexamer bound by the chaperone domains of SPT16 and MCM2

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Science China(Life Sciences) 2024年第6期67卷 1305-1307页

作者： Songlin Gan Wen-Si Yang Liting Wei Zhiguo Zhang Rui-Ming Xu key laboratory of Epigenetic Regulation and intervention Institute of BiophysicsChinese Academy of SciencesBeijing 100101China School of Life Sciences University of Chinese Academy of SciencesBeijing 100049China institute for cancer Genetics Department of Pediatrics and Department of Genetics and DevelopmentColumbia University Irving Medical CenterNew York 10032USA School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

Dear Editor,The passage of DNA replication forks during eukaryotic cell division disrupts the nucleosomes they encounter,and de novo assembly of nucleosomes onto replicated DNA must take place to restore chromatin ***... 详细信息

关键词： structure nucleosome passage

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DNA methylation clocks for estimating biological age in Chinese cohorts

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Protein & Cell 2024年第8期15卷 575-593页

作者： Zikai Zheng Jiaming Li Tianzi Liu Yanling Fan Qiao-Cheng Zhai Muzhao Xiong Qiao-Ran Wang Xiaoyan Sun Qi-Wen Zheng Shanshan Che Beier jiang Quan Zheng Cui Wang Lixiao Liu Jiale Ping Si Wang Dan-Dan Gao Jinlin Ye Kuan Yang Yuesheng Zuo Shuai Ma Yun-GuiYang Jig Qu Feng Zhang Peilin Jia Guang-Hui Liu Weiqi Zhang CAS key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China CAS key laboratory of Computational Biology Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China division of Orthopaedics Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China The Joint Innovation Center for Engineering in Medicine Quzhou Affliated Hospital of Wenzhou Medical UniversityQuzhou 324000China Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Center for Aging and CancerXuanwu HospitalCapital Medical UniversityBeijing 100053China Aging Biomarker Consortium Beijing 100101China State key laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China key laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China nstitute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing institute for Stem Cell and Regenerative Medicine Beijing 100101China State key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China National genomics Data Center Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG ***,a systematic comparison between DNA methylation data and other omics datasets has not yet been ***,available DNAm age predictors are based on datasets with limited ethnic *** address these knowledge gaps,we generated and analyzed DNA methylation datasets from two independent Chinese cohorts,revealing age-related DNAm ***,a DNA methylation aging clock(iCAS-DNAmAge)and a group of DNAm-based multi-modal clocks for Chinese individuals were developed,with most of them demonstrating strong predictive capabilities for chronological *** clocks were further employed to predict factors influencing aging *** DNAm aging clock,derived from multi-modal aging features(compositeAge-DNAmAge),exhibited a close association with multi-omics changes,lifestyles,and disease status,underscoring its robust potential for precise biological age *** findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace,providing the basis for evaluating aging intervention strategies.

关键词： DNA methylation aging clock aging age prediction

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Combining QTL Mapping and Multi-Omics Identify Candidate Genes for Nutritional Quality Traits during Grain Filling Stage in Maize

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1441-1453页

作者： Pengcheng Li Tianze Zhu Yunyun Wang Shuangyi Yin Xinjie Zhu Minggang Ji Wenye Rui Houmiao Wang Zefeng Yang Chenwu Xu Jiangsu key laboratory of Crop Genetics and Physiology Key Laboratory of Plant Functional Genomics of the Ministry of EducationJiangsu Key Laboratory of Crop Genomics and Molecular BreedingAgricultural College of Yangzhou UniversityYangzhou225009China Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops Yangzhou UniversityYangzhou225009China

The nutritional composition and overall quality of maize kernels are largely determined by the key chemical com-ponents:protein,oil,and ***,the genetic basis underlying these nutritional quality traits during grainﬁlling remains poorly *** this study,the concentrations of protein,oil,and starch were studied in 204 recombinant inbred lines resulting from a cross between DH1M and T877 at four different stages *** the traits exhibited considerable phenotypic *** the grain-ﬁlling stage,the levels of protein and starch content generally increased,whereas oil content decreased,with signiﬁcant changes observed between 30 and 40 days after *** trait locus(QTL)mapping was conducted and a total of 32 QTLs,comprising 14,12,and 6 QTLs for grain protein,oil,and starch content were detected,*** QTLs were consistently detectable across different time *** integrating QTL analysis,glo-bal gene expression proﬁling,and comparative genomics,we identiﬁed 157,86,and 54 differentially expressed genes harboring nonsynonymous substitutions between the parental lines for grain protein,oil,and starch con-tent,*** gene function annotation prioritized 15 candidate genes potentially involved in reg-ulating grain quality traits,including those encoding transcription factors(NAC,MADS-box,bZIP,and MYB),cell wall invertase,cellulose-synthase-like protein,cell division cycle protein,trehalase,auxin-responsive factor,and phloem protein *** study offers signiﬁcant insights into the genetic architecture of maize kernel nutritional quality and identiﬁes promising QTLs and candidate genes,which are crucial for the genetic enhance-ment of these traits in maize breeding programs.

关键词： Maize protein oil starch QTL mapping candidate genes

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