Genes & Diseases最新文献_第2页

Elucidating the pathogenesis of bladder cancer through single-cell chromatin accessibility and DNA methylation analysis 通过单细胞染色质可及性和DNA甲基化分析阐明膀胱癌的发病机制

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-03-03 DOI: 10.1016/j.gendis.2025.101578

Yu Xiao , Lingao Ju , Gang Wang , Wan Jin , Hongwei Peng , Zongning Zhou , Mengxue Yu , Yi Zhang , Kaiyu Qian , Xinghuan Wang

引用次数: 0

Crowdedness imposes stress on tumor metastasis in Drosophila melanogaster 拥挤对黑腹果蝇的肿瘤转移有应激作用

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-27 DOI: 10.1016/j.gendis.2025.101574

Wenzhe Li , Zhiyuan Zhang , Lealia Li Xiong , Huiyi Yu , Jiuhong Huang , Ruixiu Cao , Lei Xue

引用次数: 0

Clinical impact of the TPM1 p.Tyr221Cys variant causing hypertrophic cardiomyopathy TPM1 p.Tyr221Cys变异引起肥厚性心肌病的临床影响

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-26 DOI: 10.1016/j.gendis.2025.101575

Alessio Marinelli , Giuliana Longo , Vincenzo Cirigliano , Esther Campopiano , Clementina Dugo , Luca Ghiselli , Andrea Chiampan , Gianluca Ferri , Alessandro Costa , Stefano Bonapace , Laura Lanzoni , Giulio Molon

引用次数: 0

New genetic insights into HIV-associated neurocognitive disorder and Alzheimer's disease hiv相关神经认知障碍和阿尔茨海默病的新遗传见解

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-26 DOI: 10.1016/j.gendis.2025.101576

Hai Duc Nguyen , Woong-Ki Kim

引用次数: 0

The biological roles and molecular mechanisms of m6A reader IGF2BP1 in the hallmarks of cancer m6A读取器IGF2BP1在癌症标志中的生物学作用和分子机制

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-20 DOI: 10.1016/j.gendis.2025.101567

Li Qiu , Shourong Wu , Lei Zhang , Wenfang Li , Debing Xiang , Vivi Kasim

{"title":"The biological roles and molecular mechanisms of m6A reader IGF2BP1 in the hallmarks of cancer","authors":"Li Qiu , Shourong Wu , Lei Zhang , Wenfang Li , Debing Xiang , Vivi Kasim","doi":"10.1016/j.gendis.2025.101567","DOIUrl":"10.1016/j.gendis.2025.101567","url":null,"abstract":"<div><div>N6-methyladenosine (m6A) is the most abundant and well-investigated internal RNA modification in eukaryotic RNAs, affecting its target gene expression by controlling RNA localization, splicing, stability, and translation. m6A modifications are regulated by m6A methyltransferase complex, demethylase, and reading proteins. Insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), a member of a conserved family of single-stranded RNA-binding proteins, has recently been identified as a vital m6A reading protein. IGF2BP1 is highly expressed in various tumors and is associated with poor prognosis and treatment resistance. Furthermore, previous studies have shown that IGF2BP1 plays critical roles in regulating various cancer hallmarks, including sustained cell proliferation, cell death resistance, activation of invasion and metastasis, deregulated cellular energetics, immune evasion, and unlocking phenotypic plasticity. IGF2BP1 could promote the expression of cancer-related genes by recognizing their m6A sites, thereby altering cell characteristics, and eventually, malignancy. Therefore, IGF2BP1 might be a potential target for tumor diagnosis and anti-tumor therapeutic strategies. This review summarizes the current knowledge on the functional roles and underlying molecular mechanisms of IGF2BP1 in regulating cancer hallmarks. Moreover, we discuss the prospects of IGF2BP1 as a potential tumor diagnosis marker, as well as a potential target for an anti-tumor therapeutic strategy.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101567"},"PeriodicalIF":6.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-omics analysis of epigenetic dysregulation reveals clinical heterogeneity and evaluates the immunotherapeutic potential of lung adenocarcinoma 表观遗传失调的多组学分析揭示了临床异质性，并评估了肺腺癌的免疫治疗潜力

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-20 DOI: 10.1016/j.gendis.2025.101561

Yuqing Ren , Zaoqu Liu , Yi Yue , Siyuan Weng , Hongxia Jia , Jing Li , Ping Li , Chunya Lu , Xinwei Han , Guojun Zhang

引用次数: 0

Tumor microenvironment in osteosarcoma: From cellular mechanism to clinical therapy 骨肉瘤的肿瘤微环境：从细胞机制到临床治疗

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-20 DOI: 10.1016/j.gendis.2025.101569

Yihan Yu , Kanglu Li , Yizhong Peng , Zhicai Zhang , Feifei Pu , Zengwu Shao , Wei Wu

{"title":"Tumor microenvironment in osteosarcoma: From cellular mechanism to clinical therapy","authors":"Yihan Yu , Kanglu Li , Yizhong Peng , Zhicai Zhang , Feifei Pu , Zengwu Shao , Wei Wu","doi":"10.1016/j.gendis.2025.101569","DOIUrl":"10.1016/j.gendis.2025.101569","url":null,"abstract":"<div><div>Osteosarcoma, a prevalent primary malignant bone tumor, predominantly affects both elderly and adolescent populations and usually has an unfavorable prognosis. The specific mechanisms underlying its invasive progression remain unclear. The tumor microenvironment includes not only cancer cells but also bone-related cells, immune cells, tumor-associated nerve cells, and cell-secreted factors. The cooperative and competitive interactions among these cellular components contribute to the proliferation, progression, metastasis, and immune evasion of osteosarcoma. Alterations in bone-related cells, resulting from oncogenic changes, can rapidly increase bone density or aggravate bone loss, thereby promoting the survival of osteosarcoma cells. During the progression of osteosarcoma, genetic alterations in tumor cells lead to changes in extracellular matrix components, influencing the variation in cell-secreted factors, promoting immunosuppression within the tumor microenvironment, and consequently affecting tumor proliferation and progression. This review summarizes the roles of tumor microenvironment components in the pathogenesis of osteosarcoma and discusses existing therapeutic targets. The findings suggest potential research directions for further investigation of osteosarcoma, provide novel insights into the development of osteosarcoma, and may guide the development of more effective anti-tumor strategies.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101569"},"PeriodicalIF":6.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SIRT5 promotes the osteo-inductive potential of BMP9 by stabilizing the HIF-1α protein in mouse embryonic fibroblasts SIRT5通过稳定小鼠胚胎成纤维细胞中HIF-1α蛋白来促进BMP9的成骨诱导潜能

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-18 DOI: 10.1016/j.gendis.2025.101563

Lu Liu , Fanglin Ye , Yue Jiang , Wenting Liu , Dongmei He , Wenge He , Xiang Gao , Hang Liu , Junyi Liao , Baicheng He , Fang He

{"title":"SIRT5 promotes the osteo-inductive potential of BMP9 by stabilizing the HIF-1α protein in mouse embryonic fibroblasts","authors":"Lu Liu , Fanglin Ye , Yue Jiang , Wenting Liu , Dongmei He , Wenge He , Xiang Gao , Hang Liu , Junyi Liao , Baicheng He , Fang He","doi":"10.1016/j.gendis.2025.101563","DOIUrl":"10.1016/j.gendis.2025.101563","url":null,"abstract":"<div><div>Bone morphogenetic protein 9 (BMP9) exhibits remarkable osteogenic potential. However, the intricate mechanisms driving this function of BMP9 remain elusive. This study endeavors to investigate the potential role of sirtuin 5 (SIRT5) in enhancing BMP9's osteogenic capacity and decipher the underlying molecular pathways. To achieve this aim, we employed real-time PCR, western blotting, histochemical staining, and a cranial defect repair model to assess the impact of SIRT5 on BMP9-mediated osteogenesis. We utilized real-time PCR, western blotting, immunofluorescent staining, and immunoprecipitation assay to explore the associated mechanisms. Our results revealed that SIRT5 significantly up-regulated BMP9-induced osteogenic markers, while SIRT5 knockdown reduced their expression. Concurrently, hypoxia-inducible factor 1 subunit alpha (HIF-1α) level was increased by SIRT5, but reduced by SIRT5 knockdown. Notably, HIF-1α potentiated the SIRT5's ability to strengthen BMP9's osteogenic potential, whereas HIF-1α silencing reduced this effect, which was confirmed by bone defect repair assay. The acetylation and malonylation levels of HIF-1α were reduced by SIRT5, which may enhance its stability to promote BMP9's osteogenic effect. Conversely, SIRT5 knockdown reversed these effects and promoted the degradation of HIF-1α. Collectively, our results demonstrated that the BMP9's osteogenic potential could be promoted by SIRT5, potentially through stabilizing HIF-1α by reducing its acetylation and malonylation modification. This discovery may offer a novel strategy to accelerate bone tissue engineering by enhancing osteogenic differentiation, and it also sheds light on the possible mechanisms underlying BMP9-mediated osteogenic differentiation.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 4","pages":"Article 101563"},"PeriodicalIF":6.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactate transporter MCT4 regulates the hub genes for lipid metabolism and inflammation to attenuate intracellular lipid accumulation in non-alcoholic fatty liver disease 乳酸转运体MCT4调节脂质代谢和炎症中枢基因，以减轻非酒精性脂肪性肝病的细胞内脂质积累

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-15 DOI: 10.1016/j.gendis.2025.101554

Yannian Gou , Aohua Li , Xiangyu Dong , Ailing Hao , Jiajia Li , Han Xiang , Saidur Rahaman , Tong-Chuan He , Jiaming Fan

{"title":"Lactate transporter MCT4 regulates the hub genes for lipid metabolism and inflammation to attenuate intracellular lipid accumulation in non-alcoholic fatty liver disease","authors":"Yannian Gou , Aohua Li , Xiangyu Dong , Ailing Hao , Jiajia Li , Han Xiang , Saidur Rahaman , Tong-Chuan He , Jiaming Fan","doi":"10.1016/j.gendis.2025.101554","DOIUrl":"10.1016/j.gendis.2025.101554","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) patients have multiple metabolic disturbances, with markedly elevated levels of lactate. Lactate accumulations play pleiotropic roles in disease progression through metabolic rearrangements and epigenetic modifications. Monocarboxylate transporter 4 (MCT4) is highly expressed in hepatocytes and responsible for transporting intracellular lactate out of the cell. To explore whether elevated MCT4 levels played any role in NAFLD development, we overexpressed and silenced MCT4 in hepatocytes and performed a comprehensive <em>in vitro</em> and <em>in vivo</em> analysis. Our results revealed that MCT4 overexpression down-regulated the genes for lipid synthesis while up-regulating the genes involved in lipid catabolism. Conversely, silencing MCT4 expression or inhibiting MCT4 expression led to the accumulation of intracellular lipid and glucose metabolites, resulting in hepatic steatosis. In a mouse model of NAFLD, we found that exogenous MCT4 overexpression significantly reduced lipid metabolism and alleviated hepatocellular steatosis. Mechanistically, MCT4 alleviated hepatic steatosis by regulating a group of hub genes such as <em>Arg2</em>, <em>Olr1</em>, <em>Cd74</em>, <em>Mmp8, Irf7</em>, <em>Spp1</em>, and <em>Apoe</em>, which in turn impacted multiple pathways involved in lipid metabolism and inflammatory response, such as PPAR, HIF-1, TNF, IL-17, PI3K-AKT, Wnt, and JAK-STAT. Collectively, our results strongly suggest that MCT4 may play an important role in regulating lipid metabolism and inflammation and thus serve as a potential therapeutic target for NAFLD.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 4","pages":"Article 101554"},"PeriodicalIF":6.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expression of LINE-1 elements is required for preimplantation development and totipotency LINE-1基因的表达是着床前发育和全能性所必需的

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-02-07 DOI: 10.1016/j.gendis.2025.101555

Ru Ma , Nan Xiao , Na Liu

{"title":"Expression of LINE-1 elements is required for preimplantation development and totipotency","authors":"Ru Ma , Nan Xiao , Na Liu","doi":"10.1016/j.gendis.2025.101555","DOIUrl":"10.1016/j.gendis.2025.101555","url":null,"abstract":"<div><div>Transposable elements, long considered genomic intruders, have been found to play significant and intriguing roles during early embryonic development based on the paradigm shift that has undergone in recent years. Long interspersed element-1 (LINE-1) is the predominant class of retrotransposons with autonomous retrotransposition capabilities in mammals and has emerged as a crucial element of preimplantation development. In this review, we elucidate the expression dynamics of key transposable elements throughout preimplantation development and their contribution to the regulation of developmental progression and totipotency. We also explore the critical function of LINE-1 activation and its rich functional reservoir, which is exploited by the host to provide cis-regulatory elements and functional proteins. Particular highlights of the widespread activities in preimplantation development of LINE-1 during multiple epigenetic modifications such as DNA methylation, histone methylation, ubiquitination, and RNA methylation. The silencing complex and RNA exosome also coordinate with LINE-1 across distinct developmental stages. Accordingly, the up-regulated expression of LINE-1 retrotransposons and their protein products plays a key role in various processes, including the opening of chromatin architecture, zygotic genome activation, aging, and age-related disorders. It may reflect an effect on totipotency and pluripotency of mammalian development. Underscoring its pivotal significance, the nuanced regulation of LINE-1 illuminates its indispensable role in orchestrating the precise coordination essential for the regulation of cellular pluripotency and the intricate mechanisms of zygotic genome activation.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101555"},"PeriodicalIF":6.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0