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Ferroptosis:a critical mechanism of N^(6)-methyladenosine modification involved in carcinogenesis and tumor progression

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Science china(Life Sciences) 2024年第6期67卷 1119-1132页

作者： Qingqing Wei Changning Xue Mengna Li Jianxia Wei Lemei Zheng Shipeng Chen Yumei Duan Hongyu Deng Faqing Tang Wei Xiong Ming Zhou nhc key laboratory of carcinogenesis Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China cancer Research Institute and School of Basic Medical Sciences Central South UniversityChangsha 410078China The key laboratory of carcinogenesis and cancer invasion of the Chinese ministry of education Central South UniversityChangsha 410078China Hunan key laboratory of Oncotarget Gene Hunan Key Laboratory of Cancer MetabolismHunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China

Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid *** occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal ***,the precise regulation of ferroptosis-related molecules is mediated across multiple levels,including transcriptional,posttranscriptional,translational,and epigenetic levels.N^(6)-methyladenosine(m^(6)A)is a highly evolutionarily conserved epigenetic modification in *** m^(6)A modification is commonly linked to tumor proliferation,progression,and therapy resistance because it is involved in RNA metabolic ***,accumulating evidence suggests that dysregulated ferroptosis caused by the m^(6)A modification drives tumor *** this review,we summarized the roles of m^(6)A regulators in ferroptosis-mediated malignant tumor progression and outlined the m^(6)A regulatory mechanism involved in ferroptosis *** also analyzed the potential value and application strategies of targeting m^(6)A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.

关键词： ferroptosis m6A modification RNA methylation m^(6)A regulator tumor progression

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Role of adhesion molecules in cancer and targeted therapy

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Science china(Life Sciences) 2024年第5期67卷 940-957页

作者： Chunmei Fan Fang Xiong Shanshan Zhang Zhaojian Gong Qianjin Liao Guiyuan Li Can Guo Wei Xiong He Huang Zhaoyang Zeng nhc key laboratory of carcinogenesis and Hunan key laboratory of cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410000China Department of Histology and Embryology Xiangya School of MedicineCentral South UniversityChangsha410013China Department of Stomatology Xiangya HospitalCentral South UniversityChangsha 410078China Department of Oral and Maxillofacial Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011China key laboratory of carcinogenesis and cancer invasion of the Chinese ministry of education Cancer Research InstituteCentral South UniversityChangsha 410078China

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among *** mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor *** studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell *** this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion *** studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

关键词： adhesion molecules tumor microenvironment invasion and metastasis reshaping metabolism angiogenesis immune evasion tumor stemness therapeutic strategy

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Roles of THEM4 in the Akt pathway:a double-edged sword

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 541-556页

作者： Wen XIE Weidong LIU Lei WANG Bin ZHU Cong ZHAO Ziling LIAO Yihan LI Xingjun JIANG Jie LIU Caiping REN nhc key laboratory of carcinogenesis Department of NeurosurgeryXiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China The key laboratory of carcinogenesis and cancer invasion of the ministry of education Cancer Research InstituteSchool of Basic Medical ScienceCentral South UniversityChangsha 410078China Department of Critical Care Medicine Hainan Hospital of Chinese PLA General HospitalHainan Province Clinical Medical CenterSanya 572013China

The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of *** superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding *** studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its ***,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous *** these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially *** work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

关键词： Protein kinase B(Akt) Thioesterase superfamily member 4(THEM4) Tumor proliferation Tumor metastasis

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science china Life Sciences 2024年

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing key laboratory of carcinogenesis and Translational Research (ministry of education/Beijing) Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital &Institute Department of Gastrointestinal cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State key laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

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cancer Communications 2024年第2期44卷 226-250页

作者： Weiren Liu Huqiang Wang Qianfu Zhao Chenyang Tao Weifeng Qu Yushan Hou Run Huang Zimei Sun Guiqi Zhu Xifei Jiang Yuan Fang Jun Gao Xiaoling Wu Zhixiang Yang Rongyu Ping Jiafeng Chen Rui Yang Tianhao Chu Jian Zhou Jia Fan Zheng Tang Dong Yang Yinghong Shi Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghaiP.R.China Research Unit of Liver cancer Recurrence and Metastasis Chinese Academy of Medical SciencesBeijingP.R.China State key laboratory of Medical Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingP.R.China

Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic *** metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely ***,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat ***:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome *** on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was *** and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic *** proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA ***:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were *** metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic *** S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)*** the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)***:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing

关键词： diacylglycerol kinaseα intrahepatic cholangiocarcinoma MAPK signaling metabolic classifi-cation multiomics analysis phosphatidic acid metabolism

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Artificial intelligence-based pathological analysis of liver cancer:Current advancements and interpretative strategies

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iLIVER 2024年第1期3卷 82-89页

作者： Guang-Yu Ding Jie-Yi Shi Xiao-Dong Wang Bo Yan Xi-Yang Liu Qiang Gao Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalShanghai 200032China key laboratory of carcinogenesis and cancer invasion of ministry of education Fudan UniversityShanghai 200032China School of Computer Science and Technology Xidian UniversityXi'an 710126China School of Computer Science Shanghai Key Laboratory of Intelligent Information ProcessingFudan UniversityShanghai 200433China Institute of Biomedical Sciences Fudan UniversityShanghai 200030China State key laboratory of Genetic Engineering Fudan UniversityShanghai 200433China

In recent years,significant advances have been achieved in liver cancer management with the development of artificial intelligence(AI).AI-based pathological analysis can extract crucial information from whole slide images to assist clinicians in all aspects from diagnosis to prognosis and molecular ***,AI techniques have a“black box”nature,which means that interpretability is of utmost importance because it is key to ensuring the reliability of the methods and building trust among clinicians for actual clinical *** this paper,we provide an overview of current technical advancements in the AI-based pathological analysis of liver cancer,and delve into the strategies used in recent studies to unravel the“black box”of AI's decision-making process.

关键词： Liver cancer Artificial intelligence Pathology Interpretative model

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Chronic stress as an emerging risk factor for the development and progression of glioma

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Chinese Medical Journal 2024年第4期137卷 394-407页

作者： Lan Yi Xiang Lin Xiaoling She Wei Gao Minghua Wu Institute of Cytology and Genetics The Hengyang Key Laboratory of Cellular Stress BiologyHunan Province Cooperative Innovation Center for Molecular Target New Drug StudyHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China Department of Pathology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China key laboratory of carcinogenesis and cancer invasion of ministry of education Cancer Research InstituteCentral South UniversityChangshaHunan 410008China nhc key laboratory of carcinogenesis Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous *** with patients with other cancers,glioma patients often suffer from increased levels of psychological stress,such as anxiety and *** stress(CS)is thought to impact glioma ***,because of the complex mechanisms underlying CS and variability in individual tolerance,the role of CS in glioma remains *** review suggests a new proposal to redivide the stress system into two *** activity is dominant ***-signaling molecules produced by the neuroendocrine system are dominant *** discuss the underlying molecular mechanisms by which CS impacts *** pharmacological treatments are also summarized from the therapeutic perspective of CS.

关键词： Chronic stress Glioma Microbiota-gut-brain axis Neuroendocrine system Stress system Neural circuit

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Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma

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National Science Review 2024年第5期11卷 170-185页

作者： Yong Zhou Shanlan Mo Heyang Cui Ruifang Sun Weimin Zhang Xiaofei Zhuang Enwei Xu Hongyi Li Yikun Cheng Yongsheng Meng Meilin Liu Ting Yan Huijuan Liu Ling Zhang Bin Yang Yanfeng Xi Shubin Wang Xiaolong Cheng Shuai Cheng Li Zhihua Liu Qimin Zhan Zheng Hu Yongping Cui cancer Institute Department of Pathology Peking University Shenzhen Hospital Shenzhen Peking University-the Hong Kong University of Science and Technology(PKU-HKUST) Medical Center Institute of Cancer ResearchShenzhen Bay Laboratory key laboratory of Cellular Physiology of the ministry of education Department of Pathology Shanxi Medical University City University of Hong Kong Shenzhen Research Institute CAS key laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of Sciences Department of Surgery Faculty of Medicine The Chinese University of Hong Kong Department of Tumor Biobank Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University key laboratory of carcinogenesis and Translational Research(ministry of education/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital & Institute Research Unit of Molecular cancer Research Chinese Academy of Medical Sciences Department of Thoracic Surgery Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Department of Pathology Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University College of Letters & Science University of California Berkeley State key laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

Esophageal squamous cell carcinoma（ESCC） is a poor-prognostic cancer type with extensive intra-and inter-patient heterogeneity in both genomic variations and tumor microenvironment（TME）. However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2,accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the ***, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted ***, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.

关键词： squamous cell carcinoma heterogeneity multi-omics evolution tumor microenvironment

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Non-coding RNAs expression in SARS-CoV-2 infection:pathogenesis,clinical significance,and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第1期9卷 55-78页

作者： Xiaoxing Liu Wandi Xiong Maosen Ye Tangsheng Lu Kai Yuan Suhua Chang Ying Han Yongxiang Wang Lin Lu Yanping Bao Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)100191 BeijingChina Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research Peking University100871 BeijingChina key laboratory of Tropical Biological Resources of ministry of education School of Pharmaceutical SciencesHainan University570228 HaikouChina key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences&Yunnan Province KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences650204 KunmingYunnanChina National Institute on Drug Dependence and Beijing key laboratory of Drug Dependence Peking UniversityBeijing 100191China Institute of Brain Science and Brain-inspired Research Shandong First Medical University&Shandong Academy of Medical Sciences250117 JinanShandongChina Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina School of Public Health Peking University100191 BeijingChina

The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future *** non-coding RNAs(ncRNAs)display aberrations in the context of ***,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease *** this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long ***,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment *** addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel *** an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.

关键词： invasion therapeutic infection

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Analysis of status and countermeasures of cancer incidence and mortality in china

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Science china(Life Sciences) 2019年第5期62卷 640-647页

作者： Chunchun Wu Mengna Li Hanbing Meng Yukun Liu Weihong Niu Yao Zhou Ran Zhao Yumei Duan Zhaoyang Zeng Xiaoling Li Guiyuan Li Wei Xiong Ming Zhou key laboratory of carcinogenesis of ministry of Health of china Xiangya Hospital Central South University key laboratory of carcinogenesis and cancer invasion of ministry of education of china Cancer Research Institute and School of Basic Medicine Science Central South University

cancer is the leading cause of human deaths in the world and produces serious economic burdens. On September 12, 2018, the academic journal A cancer Journal for Clinicians published an article about the latest statistics of cancers worldwide, which provided a status report on the global burden of 36 cancers in 185 countries worldwide. cancer has also become a serious public health problem in china and caused more and more attention of the government and people in recent years. This review analyzes the incidence, mortality and prevalent trend of cancers in china, discusses the reasons behind this status, and reviews the potential countermeasures for cancer prevention and control in china.

关键词： cancer incidence mortality cancer spectrum countermeasures

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