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Decoding the intercellular communication network during tumorigenesis

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Cancer Biology & Medicine 2022年第3期19卷 265-272页

作者： Liwei An Ruixian Yu Yi Han Zhaocai Zhou State Key Laboratory of Genetic Engineering Zhongshan HospitalSchool of Life SciencesFudan UniversityShanghai 200438China Department of Medical Ultrasound Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai Engineering Research Centre of Ultrasound Diagnosis and TreatmentShanghai 200072China

Under physiological conditions,decisions about cell fate and behavior are not made by the individual cell itself,but instead strictly depend on the collective interactions of the whole cell population in the microenvironment.Thus,continuous intercellular communication influences almost all biological processes ranging from tissue/organ development,and homeostasis maintenance,to disease progression.Regarding tumorigenesis,intercellular communications between cancer cells and other cells coexist within microenvironments involving stromal cells,immune cells,and even neural cells,playing crucial roles in tumor initiation,progression,and distal metastasis.

关键词： intercellular tumorigenesis homeostasis

Diagnostic Value of GDF10 for the tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma

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当代医学科学（英文） 2024年第2期44卷 309-327页

作者： Xiao-jun WANG Jia-ping CHEN Xin-wei QIAO Wang-yang MENG Yang-wei WANG Yun-chong MENG Rong ZHAO Wei LIN Yong-de LIAO Han XIAO Pei-yuan MEI Department of Thoracic Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Thoracic Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China

Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The"R/Limma"package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the"survminer"packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens we(l)e examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

关键词： lung squamous cell carcinoma tumorigenesis bone morphogenetic protein GDF10 tumor immune microenvironment

RNA helicase MTR4 drives tumorigenesis of nasopharyngeal carcinoma by regulating the expression of key cell cycle genes

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Protein & Cell 2023年第2期14卷 149-152页

作者： Lili Yu Lei Jiang Meng Wu Wenlong Dou Kaiyuan Ji Jianlong Zhou Jinchul Kim Yang Xu Department of Cardiology Cardiovascular Key Lab of Zhejiang ProvinceThe Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Medical Oncology Key Laboratory of Cancer Prevention and InterventionMinistry of EducationThe Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Cancer Center Zhejiang UniversityHangzhou 310058China School of Basic Medical Sciences Southern Medical UniversityGuangzhou 510515China Ageing Research Center Korea Research Institute of Bioscience and BiotechnologyDeajeon 34141Korea

Dear Editor,The pathogenesis of nasopharyngeal carcinoma(NPC)is closely associated with the infection of Epstein Barr virus(EBV)(Hau et al.,2020).However,the mechanisms underlying NPC tumorigenesis remain unclear,leading to a lack of therapeutic targets to effectively treat NPC.RNA helicase MTR4,which is a compo-nent of the virus-induced cofactor complex linking viral RNA to exosome for degradation,is overexpressed in NPCs of patients.The expression levels of MTR4 are inversely correlated with the prognosis of NPC patients.

关键词： nasopharyngeal tumorigenesis

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1500-1513页

作者： Jian-Rong Sun Dong-Mei Chen Rong Huang Rui-Tao Wang Li-Qun Jia School of Clinical Medicine Beijing University of Chinese MedicineBeijing 100029China Integrated Chinese and Western Medicine Oncology China-Japan Friendship HospitalBeijing 100029China

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those i

关键词： Esophageal squamous cell carcinoma Intraepithelial neoplasia tumorigenesis Transcriptome sequencing Biomarkers Immune cell infiltration 4-nitroquinoline 1-oxid

Regulatory effects of miR-19a on MAD2 expression and tumorigenesis in gastric cancer

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Genes & Diseases 2023年第4期10卷 1180-1182页

作者： J.Bargiela-Iparraguirre J.M.Herrero N.Pajuelo-Lozano M.Perez R.Perona A.G.Quiroga C.Calés I.Sanchez-Perez Dpto.de Bioquímica.Fac.Medicina UAMMadrid 28029Spain Biomedical Research Institute of Madrid CSIC/UAMMadrid 28029Spain Cancer Stem Cell and Fibroinflammatory Microenvironment Group Chronic Diseases and Cancer Area 3-Instituto Ramón y Cajal de Investigación Sanitaria(IRYCIS)Madrid 28034Spain Unidad Asociada de Biomedicina UCLM-CSIC Madrid 28029 Spain CIBER for Rare Diseases(CIBERER) Instituto de Salud CarlosⅢ Madrid 28029Spain Dpto.de Anatomía Histología y Neurociencia.Fac.Medicina UAMMadrid 28029Spain g Dpto.de Química Inorgánica Fac.Ciencias UAMMadrid 28049Spain

Gastric cancer(GC)is worldwide the sixth most diagnosed and third leading cause of cancer deaths,with poor and late prognosis,probably due to post-surgery adjuvant treatment resistance and lack of a thorough panel of prognostic markers.We have previously shown that mitotic arrest deficient 2(MAD2,encoded by MAD2L1),a key protein of the spindle assembly checkpoint,is relevant in GC cells;its interference impairs migration and growth,while its overexpression cor-relates with tumorigenesis.

关键词： MAD2 tumorigenesis Gastric

PLEK2 promotes cancer stemness and tumorigenesis of head and neck squamous cell carcinoma via the c-Myc-mediated positive feedback loop

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Cancer Communications 2022年第10期42卷 987-1007页

作者： Xinyuan Zhao Dalong Shu Wenjuan Sun Shanshan Si Wei Ran Bing Guo Li Cui Department of Endodontics Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280P.R.China Department of Oral and Maxillofacial Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080P.R.China Department of Stomatology The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510630P.R.China Department of Oral Emergency Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280P.R.China Department of Dentistry The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080P.R.China Department of Oral and Maxillofacial Surgery Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280P.R.China Division of Oral Biology and Medicine School of DentistryUniversity of CaliforniaLos AngelesLos AngelesCalifornia 90095United States

Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the molecular events regulating HNSCC tumorigenesis remain poorly understood.Therefore,uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC.In this study,we aimed to explore the role of pleckstrin-2(PLEK2)in regulating HNSCC tumorigenesis.Methods:The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort.In vitro and in vivo experiments,including cell proliferation,colony formation,Matrigel invasion,tumor sphere formation,ALDEFLUOR,Western blotting assays and xenograft mouse models,were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells.The underlying molecular mechanisms for the tumor-promoting role of PLEK2 were elucidated using co-immunoprecipitation,cycloheximide chase analysis,ubiquitination assays,chromatin immunoprecipitation-quantitative polymerase chain reaction,luciferase reporter assays and rescue experiments.Results:The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues,and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance.Additionally,PLEK2 was important for maintaining the proliferation,invasion,epithelial-mesenchymal transition,cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells.Mechanistically,PLEK2 interacted with c-Myc and reduced the association of F-box and WD repeat domain containing 7(FBXW7)with c-Myc,thereby avoiding ubiquitination and subsequent proteasome-mediated degradation of c-Myc.Moreover,the c-Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells.c-M

关键词： c-Myc cancer stemness FBXW7 HNSCC PLEK2 positive feedback loop tumorigenesis ubiquitination-mediated degradation

lncRNA cytoskeleton regulator RNA(CYTOR):Diverse functions in metabolism,inflammation and tumorigenesis,and potential applications in precision oncology

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Genes & Diseases 2023年第2期10卷 415-429页

作者： Chunlin Ou Xiaoyun He Yong Liu Xin Zhang Department of Otolaryngology Head and Neck Surgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Pathology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Departments of Ultrasound Imaging Xiangya HospitalCentral South UniversityChangshaHunan 410008China Otolaryngology Major Disease Research Key Laboratory of Hunan ProvinceChangshaHunan 410008China Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province ChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) ChangshaHunan 410008China

Long non-coding RNAs(lncRNAs)are a novel class of non-coding RNA(ncRNA),that have been studied extensively in the field of tumor research in recent years.In the case of tumor-associated lncRNAs,lncRNA cytoskeleton regulator RNA(CYTOR)displays extensive functions in tumorigenesis,including invasion,metastasis,malignant proliferation,glycolysis,and inflammatory response.Moreover,the dysregulation of CYTOR is closely related to clinicopathological characteristics,such as tumor stage,lymph node metastasis and infiltration,and poor prognosis of tumor patients.In this review,we provide a novel strategy to summarize the biological functions and clinical value of CYTOR in tumors through an overview of the literature combined with gene set enrichment analysis.A deeper understanding of the role of CYTOR in tumorigenesis may provide new diagnostic,prognostic and therapeutic markers for human tumors.

关键词： CYTOR GSEA Inflammation LncRNAs Therapy tumorigenesis

Loss of the emei tumor suppressor promotes tumorigenesis via the JNK and Hippo pathway

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Genes & Diseases 2023年第2期10卷 329-331页

作者： Shuai Yang Yifan Guo Xianjue Ma Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province School of Life SciencesWestlake UniversityHangzhouZhejiang 310024China Westlake Laboratory of Life Sciences and Biomedicine HangzhouZhejiang 310024China Institute of Biology Westlake Institute for Advanced StudyHangzhouZhejiang 310024China

Mutations in the Ras oncogene are the most frequently cancer alterations, occurring in more than 30% of all human cancers. The failures in the development of successful clinical inhibitors against Ras have made Ras as a “undruggable” target. The major reason is lack of a systematic understanding of oncogenic cooperation between Ras activation and mutation of related tumor suppressor genes.1 The genetic techniques available in the Drosophila melanogaster allow analysis of the behavior of cells with distinct mutations, making this the ideal model organism to dissect oncogenic cooperation induced tumorigenesis.2 The exact same mutation, e.g., RasV12, was mimicked in the Drosophila, which enables us to perform large scale genetic screens, aiming to unearth novel tumor suppressors that can synergistically enhance RasV12-related tumor growth.

关键词： suppressor tumorigenesis alterations

The role of ALDH2 in tumorigenesis and tumor progression:Targeting ALDH2 as a potential cancer treatment

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Acta Pharmaceutica Sinica B 2021年第6期11卷 1400-1411页

作者： Hong Zhang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteSun Yat-sen University Cancer CenterGuangzhou510060China

A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2(ALDH2).The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported.Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types.Furthermore,the ALDH2*2 polymorphism(rs671) is the most common single nucleotide polymorphism(SNP) in Asia.Epidemiological studies associate ALDH2*2 with tumorigenesis and progression.This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence,progression,and treatment of tumors in various types of cancer.Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.

关键词： ALDH2 Polymorphism Cancer tumorigenesis Progression Cancer therapy Acetaldehyde Metastasis