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Hippo-YAP/TAZ signaling in breast cancer:Reciprocal regulation of microRNAs and implications in precision medicine

Genes & Diseases 2024年第2期11卷 760-771页

作者： Farzad Sadri Seyede fatemeh Hosseini Zohreh Rezaei Mohammad Fereidouni Student Research committee Birjand University of Medical SciencesBirjand ***Iran Tabas School of Nursing Birjand University of Medical SciencesBirjand ***Iran Department of biology University of Sistan and BaluchestanZahedan ***Iran Cellular and Molecular Research Center Birjand University of Medical SciencesBirjand ***Iran

Breast cancer is a molecularly heterogeneous disease and the most common female malignancy.In recent years,therapy approaches have evolved to accommodate molecular diversity,with a focus on more biologically based therapies to minimize negative consequences.To regulate cell fate in human breast cells,the Hippo signaling pathway has been associated with the alpha subtype of estrogen receptors.This pathway regulates tissue size,regeneration,and healing,as well as the survival of tissue-specific stem cells,proliferation,and apoptosis in a variety of organs,allowing for cell differentiation.Hippo signaling is mediated by the kinases MST1,MST2,LATS1,and LATS2,as well as the adaptor proteins SAV1 and MOB.These kinases phosphorylate the downstream effectors of the Hippo pathway,yes-associated protein(YAP),and transcriptional coactivator with PDZ-binding motif(TAZ),suppressing the expression of their downstream target genes.The Hippo signaling pathway kinase cascade plays a significant role in all cancers.Understanding the principles of this kinase cascade would prevent the occurrence of breast cancer.In recent years,small noncoding RNAs,or microRNAs,have been implicated in the development of several malignancies,including breast cancer.The interconnections between miRNAs and Hippo signaling pathway core proteins in the breast,on the other hand,remain poorly understood.In this review,we focused on highlighting the Hippo signaling system,its key parts,its importance in breast cancer,and its regulation by miRNAs and other related pathways.

关键词： Breast cancer Hippo signaling Large tumor suppressor kinase 1 microRNAs PDZ-binding motif Yes-associated protein

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Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma

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Frontiers of Medicine 2024年第2期18卷 375-393页

作者： Fu’an Xie Yujia Niu Lanlan Lian Yue Wang Aobo Zhuang Guangting Yan Yantao Ren Xiaobing Chen Mengmeng Xiao Xi Li Zhe Xi Gen Zhang Dongmei Qin Kunrong Yang Zhigang Zheng Quan Zhang Xiaogang Xia Peng Li Lingwei Gu Ting Wu Chenghua Luo Shu-Hai Lin Wengang Li cancer Research Center Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361102China State Key Laboratory of Cellular Stress biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen361102China Xiamen University Research Center of Retroperitoneal Tumor committee of Oncology Society of Chinese Medical Association Xiamen UniversityXiamen361102China Department of Laboratory Medicine Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361102China Department of Retroperitoneal Tumor Surgery Peking University International HospitalBeijing102206China School of Public Health Harvard UniversityBostonMA02115USA Laboratory of Biochemistry and Molecular biology Research Department of Clinical LaboratoryFujian Medical University Cancer HospitalFuzhou350014China Surgery Department Affiliated Fuzhou First Hospital of Fujian Medical UniversityFuzhou350009China National Institute for Data Science in Health and Medicine Xiamen UniversityXiamen361102China Department of Hepatobiliary Surgery Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen361102China

Retroperitoneal liposarcoma(RLPS)is the main subtype of retroperitoneal soft sarcoma(RSTS)and has a poor prognosis and few treatment options,except for surgery.The proteomic and metabolic profiles of RLPS have remained unclear.The aim of our study was to reveal the metabolic profile of RLPS.Here,we performed proteomic analysis(n=10),metabolomic analysis(n=51),and lipidomic analysis(n=50)of retroperitoneal dedifferentiated liposarcoma(RDDLPS)and retroperitoneal well-differentiated liposarcoma(RWDLPS)tissue and paired adjacent adipose tissue obtained during surgery.Data analysis mainly revealed that glycolysis,purine metabolism,pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue,whereas the tricarboxylic acid(TCA)cycle,lipid absorption and synthesis,fatty acid degradation and biosynthesis,as well as glycine,serine,and threonine metabolism were downregulated.Of particular importance,the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway(PPP)inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib.Our study not only describes the metabolic profiles of RDDLPS and RWDLPS,but also offers potential therapeutic targets and strategies for RLPS.

关键词： RLPS proteomics metabolomics lipidomics metabolism

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Oncogenic MORC2 in cancer development and beyond

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Genes & Diseases 2024年第2期11卷 861-873页

作者： Shan Zhang Ayao Guo Huan Wang Jia Liu Chenshuang Dong Junyi Ren Guiling Wang Key Laboratory of Cell biology Department of Cell BiologyMinistry of Public Health and Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyangLiaoning 110122China Department of Breast Surgery The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China

Microrchidia CW-type zinc finger 2(MORC2)is a member of the MORC superfamily of nuclear proteins.Growing evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also plays a key in human disease and tumor development by regulating the expression of downstream oncogenes or tumor suppressors.The present review provides an updated overview of MORC2 in the aspect of cancer hallmark and therapeutic resistance and summarizes its upstream regulators and downstream target genes.This systematic review may provide a favorable theoretical basis for emerging players of MORC2 in tumor development and new insight into the potential clinical application of basic science discoveries in the future.

关键词： cancer development Hallmarks of cancer MORC2 Therapeutic target Treatment resistance

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Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer:A systematic review

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 197-213页

作者： Eman Al-Balushi Amina Al Marzouqi Shima Tavoosi Amir Hossein Baghsheikhi Arash Sadri Leyla Sharifi Aliabadi Mohammad-Mahdi Salarabedi Syed Azizur Rahman Nabeel Al-Yateem Alireza Mosavi Jarrahi Aram Halimi Mohammad Ahmadvand Wael M Abdel-Rahman College of Health Sciences University of SharjahSharjah 27272United Arab Emirates Department of biology Faculty of SciencesUniversity of IsfahanIsfahan 81746-73441Iran Department of biology Science and Research BranchIslamic Azad UniversityTehran 11365/4435Iran Students’Scientific Research Center Tehran University of Medical SciencesTehran ***Iran Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center Research Institute for OncologyHematologyand Cell TherapyTehran University of Medical SciencesTehran ***Iran Student Research committee School of MedicineShahid Beheshti University of Medical SciencesTehran ***Iran Department of Nursing University of SharjahSharjah 27272United Arab Emirates cancer Research Centre Shahid Beheshti University of Medical SciencesTehran ***Iran Department of Medical Laboratory Sciences University of SharjahSharjah 27272United Arab Emirates

BACKGROUND Colorectal cancer(CRC)is the third most frequent and the second most fatal cancer.The search for more effective drugs to treat this disease is ongoing.A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic strategies.Ubiquitin-specific peptidases(USPs),the largest group of the deubiquitinase protein family,have long been implicated in various cancers.There have been numerous studies on the role of USPs in CRC;however,a comprehensive view of this role is lacking.AIM To provide a systematic review of the studies investigating the roles and functions of USPs in CRC.METHODS We systematically queried the MEDLINE(via PubMed),Scopus,and Web of Science databases.RESULTS Our study highlights the pivotal role of various USPs in several processes implicated in CRC:Regulation of the cell cycle,apoptosis,cancer stemness,epithelial–mesenchymal transition,metastasis,DNA repair,and drug resistance.The findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in CRC.The dysregulation of USPs in CRC contributes to drug resistance through multiple mechanisms.CONCLUSION Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC.

关键词： Ubiquitin-specific peptidases Colorectal cancer Deubiquitinase protein family Drug target discovery Biomarker discovery

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A chromosome-level genome of electric catfish(Malapterurus electricus)provided new insights into order Siluriformes evolution

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Marine Life Science & Technology 2024年第1期6卷 1-14页

作者： Meiru Liu Yue Song Suyu Zhang Lili Yu Zengbao Yuan Hengjia Yang Mengqi Zhang Zhuocheng Zhou Inge Seim Shanshan Liu Guangyi Fan Huanming Yang College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China BGI-Qingdao BGI-ShenzhenQingdao 266555China BGI-Shenzhen Shenzhen 518083China Professional committee of Native Aquatic Organisms and Water Ecosystem of China Fisheries Association Beijing 100125China Integrative biology Laboratory College of Life SciencesNanjing Normal UniversityNanjing 210023China State Key Laboratory of Agricultural Genomics BGI-ShenzhenShenzhen 518083China

The electric catfish(Malapterurus electricus),belonging to the family Malapteruridae,order Siluriformes(Actinopterygii:Ostariophysi),is one of the six branches that has independently evolved electrical organs.We assembled a 796.75 Mb M.electricus genome and anchored 88.72%sequences into 28 chromosomes.Gene family analysis revealed 295 expanded gene families that were enriched on functions related to glutamate receptors.Convergent evolutionary analyses of electric organs among different lineage of electric fishes further revealed that the coding gene of rho guanine nucleotide exchange factor 4-like(arhgef4),which is associated with G-protein coupled receptor(GPCR)signaling pathway,underwent adaptive parallel evolution.Gene identification suggests visual degradation in catfishes,and an important role for taste in environmental adaptation.Our findings fill in the genomic data for a branch of electric fish and provide a relevant genetic basis for the adaptive evolution of Siluriformes.

关键词： Electric fish Karyotype analysis Convergent evolution Environmental adaptation Historical effective population size

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Exploring the relationship between ambient sulfur dioxide and semen quality parameters:A systematic review and meta-analysis

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Asian pacific Journal of Reproduction 2024年第1期13卷 12-21页

作者： Seyed Sobhan Bahreiny Mojtaba Aghaei Mohammad Reza Dabbagh Hamid Ghorbani Moslem Javidan Reza Mohammadpour Fard Student Research committee Ahvaz Jundishapur University of Medical SciencesAhvazIran Medical Basic Sciences Research Institute Physiology Research CenterDepartment of PhysiologySchool of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran Department of biology Faculty of ScienceShahid Chamran University of AhvazAhvazIran Department of Immunology Faculty of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran

Objective:To investigate the relationship between ambient sulfur dioxide(SO2)exposure and semen quality parameters.Methods:A systematic literature search was conducted to identify relevant studies investigating the association between SO2 exposure and semen quality parameters.This search encompassed the timeframe from January 2000 to May 2023 and included electronic databases such as Web of Science,Google Scholar,PubMed,Cochrane,and Scopus.Pooled effect estimates with 95%confidence intervals(CI)were calculated using percent changes(PC).The meta-analysis included seven studies with 6711 participants and 15087 semen samples.Results:The results revealed a significant negative association between ambient SO2 exposure and certain semen quality parameters.In particular,SO2 exposure was associated with a significant decrease in progressive motility(PC=0.032;95%CI:-0.063 to-0.001;P=0.044)and sperm concentration(PC=-0.020;95%CI:-0.036 to-0.005;P=0.012).However,no statistically significant associations were observed for total sperm count(PC=-0.038;95%CI:-0.079 to 0.003;P=0.070),seminal fluid volume(PC=-0.009;95%CI:-0.048 to-0.030;P=0.662)and sperm motility(PC=-0.17;95%CI:-0.363 to 0.022;P=0.830).In addition,the results of the subgroup analysis revealed specific variables that were associated with the decrease in relevant sperm parameters.Conclusions:This systematic review and meta-analysis provides compelling evidence supporting a consistent negative association between exposure to ambient SO2 and semen quality parameters.

关键词： Semen quality Sulfur dioxide Ambient air pollution Meta-analysis

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A novel heterozygous SF1/NR5A1 gene variant causes 46,XY DSD-gonadal dysgenesis with hypergonadotropic hypogonadism without adrenal insufficiency

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Genes & Diseases 2024年第4期11卷 128-130页

作者： Luis Ramos Department of Reproductive biology Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubirdnTlalpanMexico City 14080Mexico

Steroidogenic factor 1(SF1/NR5A1;nuclear receptor subfamily 5 group A member 1)is an essential orphan protein involved in gonadal embryogenesis,sex determination,and reproductive endocrinology.

关键词： insufficiency determination gonadal

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Cryptic diversity and rampant hybridization in annual gentians on the Qinghai-Tibet Plateau revealed by population genomic analysis

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Plant Diversity 2024年第2期46卷 194-205页

作者： Peng-Cheng Fu Qiao-Qiao Guo Di Chang Qing-Bo Gao Shan-Shan Sun School of Life Science Luoyang Normal UniversityLuoyang 471934PR China Key Laboratory of Adaptation and Evolution of Plateau Biota Northwest Institute of Plateau BiologyChinese Academy of SciencesXining 810001PR China

Understanding the evolutionary and ecological processes involved in population differentiation and speciation provides critical insights into biodiversity formation. In this study, we employed 29,865 single nucleotide polymorphisms(SNPs) and complete plastomes to examine genomic divergence and hybridization in Gentiana aristata, which is endemic to the Qinghai-Tibet Plateau(QTP) region. Genetic clustering revealed that G. aristata is characterized by geographic genetic structures with five clusters(West, East, Central, South and North). The West cluster has a specific morphological character(i.e., blue corolla) and higher values of FSTcompared to the remaining clusters, likely the result of the geological barrier formed by the Yangtze River. The West cluster diverged from the other clusters in the Early Pliocene;these remaining clusters diverged from one another in the Early Quaternary. Phylogenetic reconstructions based on SNPs and plastid data revealed substantial cyto-nuclear conflicts. Genetic clustering and D-statistics demonstrated rampant hybridization between the Central and North clusters,along the Bayankala Mountains, which form the geological barrier between the Central and North clusters. Species distribution modeling demonstrated the range of G. aristata expanded since the Last Interglacial period. Our findings provide genetic and morphological evidence of cryptic diversity in G. aristata, and identified rampant hybridization between genetic clusters along a geological barrier.These findings suggest that geological barriers and climatic fluctuations have an important role in triggering diversification as well as hybridization, indicating that cryptic diversity and hybridization are essential factors in biodiversity formation within the QTP region.

关键词： Gentiana aristata Hybrid zone Qinghai-Tibet Plateau Plastome Nuclear SNPs

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The First-in-Human Whole-Body Dynamic Pharmacokinetics Study of Aptamer

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Research 2024年第1期2023卷 119-130页

作者： Ding Ding Haitao Zhao Dali Wei Qinglai Yang Cai Yang Ruowen Wang Yumei Chen Lianghua Li Shuxian An Qian Xia Gang Huang Jianjun Liu Zeyu Xiao Weihong Tan Institute of Molecular Medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of Medicineand College of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Nuclear Medicine Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Center for Molecular Imaging Probes Cancer Research InstituteUniversity of South ChinaHengyangHunan 421001China The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangshaHunan 410082China Shanghai Key Laboratory of Molecular Imaging Shanghai University of Medicine and Health SciencesShanghai 201318China Department of Pharmacology and Chemical biology Shanghai Jiao Tong University School of MedicineShanghai200127China

Serving as targeting ligands,aptamers have shown promise in precision medicine.However,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical translation.To bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled aptamers.The specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in vitro.Further preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human body.Taking advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.

关键词： metabolism dosage Whole

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Stabilization and detection of labile reaction intermediates in supramolecular containers

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Chinese Chemical Letters 2024年第6期35卷 47-52页

作者： Rui Wang Yang Liang Julius Rebek Jr. Yang Yu Center for Supramolecular Chemistry&Catalysis and Department of Chemistry College of ScienceShanghai UniversityShanghai 200444China Skaggs Institute for Chemical biology and Department of Chemistry The Scripps Research InstituteLa JollaCA 92037United States

Detection and observation of reactive intermediates is an essential step in investigation of reaction pathways.However,most reactive intermediates are unstable and present at low concentrations;their short lifetimes make them difficult to detect and characterize.Supramolecular containers offer opportunities for the stabilization and characterization of those labile species,through isolation from the media and protection inside the cavity of the host.In this review,we summarize the examples of labile reaction intermediates that are stabilized and characterized with the help of supramolecular containers.The container compounds include carcerands,deep cavitands and amide naphthotubes.We focus on unstable guest species-cyclobutadiene,benzocyclopropenone,o-benzyne,1,2,4,6-cycloheptatetraene,anti-Bredt's olefin,fluorophenoxycarbene,O-acylisoamide,and hemiaminalthat act as intermediates in certain organic reactions.

关键词： Supramolecular containers Reaction intermediates Labile species stabilization Short-lived species detection Supramolecular chemistry

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