Genes & Diseases最新文献

{"title":"Multi-omics analysis of epigenetic dysregulation reveals clinical heterogeneity and evaluates the immunotherapeutic potential of lung adenocarcinoma","authors":"Yuqing Ren , Zaoqu Liu , Yi Yue , Siyuan Weng , Hongxia Jia , Jing Li , Ping Li , Chunya Lu , Xinwei Han , Guojun Zhang","doi":"10.1016/j.gendis.2025.101561","DOIUrl":"10.1016/j.gendis.2025.101561","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101561"},"PeriodicalIF":6.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166636","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}

{"title":"Tumor microenvironment in osteosarcoma: From cellular mechanism to clinical therapy","authors":"Yihan Yu ,&nbsp;Kanglu Li ,&nbsp;Yizhong Peng ,&nbsp;Zhicai Zhang ,&nbsp;Feifei Pu ,&nbsp;Zengwu Shao ,&nbsp;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}

{"title":"SIRT5 promotes the osteo-inductive potential of BMP9 by stabilizing the HIF-1α protein in mouse embryonic fibroblasts","authors":"Lu Liu ,&nbsp;Fanglin Ye ,&nbsp;Yue Jiang ,&nbsp;Wenting Liu ,&nbsp;Dongmei He ,&nbsp;Wenge He ,&nbsp;Xiang Gao ,&nbsp;Hang Liu ,&nbsp;Junyi Liao ,&nbsp;Baicheng He ,&nbsp;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}

{"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 ,&nbsp;Aohua Li ,&nbsp;Xiangyu Dong ,&nbsp;Ailing Hao ,&nbsp;Jiajia Li ,&nbsp;Han Xiang ,&nbsp;Saidur Rahaman ,&nbsp;Tong-Chuan He ,&nbsp;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}

{"title":"Expression of LINE-1 elements is required for preimplantation development and totipotency","authors":"Ru Ma ,&nbsp;Nan Xiao ,&nbsp;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}

{"title":"Identification of POLQ as a chromosomal instability-associated biomarker for hepatocellular carcinoma","authors":"Ying Cai ,&nbsp;Na Wang ,&nbsp;Qiang Liu ,&nbsp;Yidi Wang ,&nbsp;Dina Liu ,&nbsp;Jing Liu ,&nbsp;Hengyu Zhou","doi":"10.1016/j.gendis.2025.101553","DOIUrl":"10.1016/j.gendis.2025.101553","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 6","pages":"Article 101553"},"PeriodicalIF":6.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670258","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}

{"title":"Deciphering the molecular landscape of oral squamous cell carcinoma: Novel biomarkers and therapeutic targets","authors":"Qingyue Xiao ,&nbsp;Kun Wang ,&nbsp;Xiang Gao ,&nbsp;Ping Ji ,&nbsp;Jinlin Song","doi":"10.1016/j.gendis.2025.101552","DOIUrl":"10.1016/j.gendis.2025.101552","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101552"},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166692","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}

{"title":"HOPX inhibits skin cutaneous melanoma growth and induces macrophage M1 polarization","authors":"Xiwen Zhang ,&nbsp;Song He ,&nbsp;Qing Zhang ,&nbsp;Zhonghao Ji ,&nbsp;Jianze Zheng ,&nbsp;Luyao Cui ,&nbsp;Bao Yuan ,&nbsp;Jian Chen ,&nbsp;Yu Ding","doi":"10.1016/j.gendis.2025.101550","DOIUrl":"10.1016/j.gendis.2025.101550","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101550"},"PeriodicalIF":6.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166691","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}

{"title":"Genetically predicted blood metabolites mediate the association between immune cell characteristics and urolithiasis: A Mendelian randomization study and mediation analysis","authors":"Chengcheng Wei ,&nbsp;Jiatai He ,&nbsp;Jun Wen ,&nbsp;Shunyao Wang ,&nbsp;Mengjia Shi ,&nbsp;Juan Hu ,&nbsp;Huanhuan Tan ,&nbsp;Jinjun Guo ,&nbsp;Xiaosong Li","doi":"10.1016/j.gendis.2025.101547","DOIUrl":"10.1016/j.gendis.2025.101547","url":null,"abstract":"<div><div>Urolithiasis, a disease characterized by the formation of urinary stones, is influenced by immune system dysregulation and metabolic factors. This study investigated the interplay between specific immune cell characteristics and blood metabolites in urolithiasis based on Mendelian randomization. We further explored the potential mediating effects of genetically predicted blood metabolites based on mediation analysis. We employed a two-sample Mendelian randomization analysis to examine the association between immune cell properties, blood metabolites, and urolithiasis risk. Genetic instruments for immune cell characteristics and blood metabolites were used to assess causal relationships and mediating pathways. Our results indicate that 10 immune cell characteristics had a unidirectional causal association with urolithiasis risk. We also detected 13 blood metabolites associated with urolithiasis. We identified 4 pathways through which genetically predicted blood metabolites partly mediated the association between specific immune cell characteristics and urolithiasis risk. This suggests potential mechanistic links where altered blood metabolites may play a role in developing urolithiasis through immune system modulation. This Mendelian randomization study highlights the complex relationship between immune responses, blood metabolites, and urolithiasis. The findings underscore the importance of considering both immune cell features and metabolic factors in understanding the pathogenesis of urolithiasis, offering insights into novel therapeutic targets and diagnostic strategies for this disorder.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101547"},"PeriodicalIF":6.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335779","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}

{"title":"Autophagy-induced NR2F1 activation promotes the apoptosis of lens epithelial cells and facilitates cataract-associated fibrosis through targeting STAT3","authors":"Hangjia Zuo ,&nbsp;Xianyang Liu ,&nbsp;Bingjing Lv ,&nbsp;Ning Gao ,&nbsp;Miaomiao Du ,&nbsp;Xiang Gao ,&nbsp;Yongguo Xiang ,&nbsp;Rongxi Huang ,&nbsp;Meiting Lin ,&nbsp;Yakun Wang ,&nbsp;Yonglin Chen ,&nbsp;Hong Cheng ,&nbsp;Tong Zhang ,&nbsp;Shijie Zheng ,&nbsp;Wenjuan Wan ,&nbsp;Ke Hu","doi":"10.1016/j.gendis.2025.101549","DOIUrl":"10.1016/j.gendis.2025.101549","url":null,"abstract":"<div><div>Cataracts, a widely prevalent ocular pathology, engender visual impairment and emerge as a primary etiological factor contributing to ocular blindness. Substantial evidence substantiates that epithelial–mesenchymal transition stands prominently among the pivotal causative factors associated with this debilitating condition. However, the underlying mechanism remains unclear. In the present study, we analyzed the single-cell data and found that the mRNA expression of nuclear receptor subfamily 2 group F member 1 (NR2F1/COUP-TFI) was notably decreased in fibrocytes compared with epithelium. Interestingly, we observed a significant up-regulation of NR2F1 protein in the anterior subcapsular cataract mice model and transforming growth factor-β1 (TGF-β1)-treated SRA01/04 cells. Furthermore, we found that TGF-β1 stimulation disrupted the balance of autophagy, leading to impaired degradation and increased protein levels of NR2F1 in SRA01/04 cells. Subsequently, after anterior chamber injection of NR2F1 adeno-associated virus in anterior subcapsular cataract mice, the development of fibrosis was alleviated. <em>In vitro</em>, the knockdown of NR2F1 in SRA01/04 also mitigated the TGF-β1-induced epithelial–mesenchymal transition. Mechanically, NR2F1 proteins directly interacted with the promoter region of STAT3 and orchestrated the up-regulation of phosphorylated STAT3 (p-STAT3), thereby facilitating the apoptosis and migration of SRA01/04 cells via the JAK1/STAT3 pathway, resulting in epithelium fibrosis and cataracts. Furthermore, inhibition of p-STAT3 obviously attenuated apoptosis and fibrosis of SRA01/04 cells. Collectively, our study provides a novel therapeutic target for cataracts and offers insight into the underlying mechanism of the epithelial–mesenchymal transition of cataracts.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101549"},"PeriodicalIF":6.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366328","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}