Genes & Diseases最新文献

{"title":"MSC-EVs alleviate osteoarthritic joint pain and degeneration by suppressing IL-1β/NGF signaling","authors":"Kristeen Ye Wen Teo , Chengming Wen , Raymond Chung Wen Wong , Wei Seong Toh","doi":"10.1016/j.gendis.2025.101981","DOIUrl":"10.1016/j.gendis.2025.101981","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101981"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924505","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":"Elevated TOR1B expression predicts poor survival outcomes in patients with breast cancer","authors":"Kun Fang , Suxiao Jiang , Zhengjie Xu , Meng Luo , Yinling Ma , Changsheng Yan","doi":"10.1016/j.gendis.2025.101826","DOIUrl":"10.1016/j.gendis.2025.101826","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101826"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024255","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":"MFAP2 promotes metastasis and drug resistance by regulating epithelial-to-mesenchymal transition through EGFR signaling pathway in colorectal cancer cells","authors":"Zhicheng He ,&nbsp;Yuanzhi Chen ,&nbsp;Shuting Yang ,&nbsp;Cheng Chen ,&nbsp;Yingying He ,&nbsp;Shubai Liu","doi":"10.1016/j.gendis.2025.101800","DOIUrl":"10.1016/j.gendis.2025.101800","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a prevalent condition, with metastasis spread as the primary cause of mortality. However, MFAP2 function in CRC progression and its regulatory mechanisms in metastasis remain poorly understood. To investigate the status of MFAP2, an extensive analysis was conducted using multiple clinical databases and transcriptomic data from CRC metastasis patients’ tissues and several CRC cell lines. The efficacy of standard first-line chemotherapy drugs (5-fluorouracil, irinotecan, and oxaliplatin) were evaluated for any potential drug resistance. Virtual screening and molecular docking were used to identify potential inhibitory compounds that could be effective against CRC. Moreover, MFAP2 expression was found to be significantly higher in CMS4 CRC patients compared to those with other subtypes. This elevation in MFAP2 correlated with both tumor stromal score and tumor purity. Reducing MFAP2 expression led to a significantly decline in the functional capabilities of CRC cells and heightened their sensitivity to standard chemotherapy treatments. Results have identified MFAP2 as a key regulator in the metastasis of CRC, influencing processes like epithelial-to-mesenchymal transition through the EGFR-AKT-STAT3 signaling pathway. Therefore, MFAP2 emerges as a promising therapeutic target for anti-tumor efforts. Notable, three compounds were discovered that effectively bind and down-regulate MFAP2, which significantly impairs tumor cells migration. These findings revealed new functions of MFAP2, suggesting it plays a vital role in driving epithelial-to-mesenchymal transition, metastasis, and chemotherapy resistance in CRC. This provides a fresh perspective for developing treatment strategies. Overall, targeting MFAP2 may offer a more effective therapeutic option for CRC patients with CMS4.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101800"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170379","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":"TGIF2-mediated HMGB3 overexpression promotes esophageal squamous cell carcinoma proliferation and metastasis through TLR3/TGF-β signaling","authors":"Liaoran Niu ,&nbsp;Wanli Yang ,&nbsp;Wei Zhou ,&nbsp;Lili Duan ,&nbsp;Qi Wang ,&nbsp;Xiaoqian Wang ,&nbsp;Yiding Li ,&nbsp;Chengchao Xu ,&nbsp;Yujie Zhang ,&nbsp;Jinqiang Liu ,&nbsp;Jian Zhang ,&nbsp;Daiming Fan ,&nbsp;Jianyong Zheng ,&nbsp;Liu Hong","doi":"10.1016/j.gendis.2025.101987","DOIUrl":"10.1016/j.gendis.2025.101987","url":null,"abstract":"<div><div>Proliferation and metastasis are the core malignant characteristics in esophageal squamous cell carcinoma (ESCC) that contribute to poor prognosis. However, the mechanisms underlying cell proliferation and metastasis remain elusive. We explored the function of high-mobility group box (HMGB3) in promoting ESCC progression. HMGB3 expression in ESCC tissues and cell lines was quantified using quantitative PCR, Western blotting, and immunohistochemistry. The proliferative and migratory characteristics of ESCC cells were assessed using <em>in vitro</em> and <em>in vivo</em> assays, respectively. An RNA sequencing analysis was conducted to identify the downstream signaling pathways of HMGB3. Co-immunoprecipitation was performed to identify HMGB3-interacting proteins. HMGB3 transcriptional regulation was investigated using luciferase reporter and chromatin immunoprecipitation assays. Elevated levels of HMGB3 were observed in both patient-derived ESCC tissues and ESCC cell lines and were correlated with poor patient prognosis. HMGB3 up-regulation promoted ESCC proliferation and metastasis, whereas HMGB3 down-regulation inhibited these processes. Mechanistically, homeodomain protein transforming growth factor beta (TGF-β)-induced factor homeobox 2 (TGIF2) transcriptionally up-regulates HMGB3. HMGB3 subsequently activates TGF-β signaling through its regulation of and interaction with toll-like receptor 3 (TLR3), ultimately promoting ESCC proliferation and metastasis. Clinically, HMGB3 expression was positively correlated with TGIF2 and TGF-β, and patients with ESCC who positively co-expressed TGIF2/HMGB3, HMGB3/TGF-β, or TGIF2/TGF-β exhibited poor prognosis. The functional role of HMGB3 in ESCC proliferation and metastasis was illustrated in our research. Targeting the TGIF2/HMGB3/TLR3/TGF-β axis has the potential to serve as a promising therapeutic approach.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 3","pages":"Article 101987"},"PeriodicalIF":9.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170451","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":"Molecular profiling unveils genetic complexity and identifies potential new driver mechanisms in head and neck paragangliomas","authors":"Sara Mellid ,&nbsp;Eduardo Caleiras ,&nbsp;Ángel M. Martínez-Montes ,&nbsp;Alicia Arenas ,&nbsp;Scherezade Jiménez ,&nbsp;María Monteagudo ,&nbsp;Rocío Letón ,&nbsp;Roberta Radu ,&nbsp;Ruth Álvarez-Díaz ,&nbsp;Ester Arroba ,&nbsp;Alberto Diaz-Talavera ,&nbsp;Natalia Martínez-Puente ,&nbsp;Cristina Álvarez-Escolá ,&nbsp;Marta Pineda ,&nbsp;Milagros Balbín ,&nbsp;Fátima Al-Shahrour ,&nbsp;Cristina Rodriguez-Antona ,&nbsp;Cristina Montero-Conde ,&nbsp;Luis J. Leandro-García ,&nbsp;Emiliano Honrado ,&nbsp;Alberto Cascón","doi":"10.1016/j.gendis.2025.101705","DOIUrl":"10.1016/j.gendis.2025.101705","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101705"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419778","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":"UBR5 regulates the progression of colorectal cancer cells through Snail-induced epithelial–mesenchymal transition","authors":"Xinyue Zhao ,&nbsp;Ruiying Liu ,&nbsp;Zhihui Han ,&nbsp;Zehao Li ,&nbsp;Ling Mei ,&nbsp;Yuyang Liu ,&nbsp;Xueqi Fu ,&nbsp;Yue Jin","doi":"10.1016/j.gendis.2025.101679","DOIUrl":"10.1016/j.gendis.2025.101679","url":null,"abstract":"<div><div>Snail is a core inducer of epithelial-to-mesenchymal transition. Here, we show that UBR5 promotes ubiquitin-mediated degradation of Snail and regulates the progression of colorectal cancer cells through its E3 ubiquitin ligase function. UBR5 specifically binds to Snail <em>in vitro</em>, but not Slug, and its degradation depends on snail phosphorylation. Depletion of endogenous UBR5 causes Snail protein accumulation, epithelial-to-mesenchymal transition, and tumor invasion in colorectal cancer cells. Conversely, the overexpression of UBR5 reduces Snail protein abundance and cellular invasiveness. The activity-deficient mutant UBR5 C2768S disrupts its binding and degradation to Snail, thereby losing the ability to regulate epithelial-to-mesenchymal transition in colorectal cancer cells. UBR5 is lowly expressed in human colorectal cancer versus normal tissues, and high UBR5 levels correlate with favorable prognosis, suggesting that UBR5 sustains the epithelial state and inhibits cancer progression. These findings establish the UBR5-Snail axis as a mechanism of post-translational regulation of epithelial-to-mesenchymal transition and colorectal cancer metastasis.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101679"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732984","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":"The advancements in organoids: Potential and challenges in researching the esophagus and esophageal squamous cell carcinoma","authors":"Xinxin Li ,&nbsp;Zhuo Wang ,&nbsp;Yongpan Liu ,&nbsp;Jiaying Zhang ,&nbsp;Lijia Zhang ,&nbsp;Yi Li ,&nbsp;Xiaolu An ,&nbsp;Yihui Yang ,&nbsp;Ruixuan Yu ,&nbsp;Meng Zhao ,&nbsp;Kuancan Liu","doi":"10.1016/j.gendis.2025.101680","DOIUrl":"10.1016/j.gendis.2025.101680","url":null,"abstract":"<div><div>Esophageal squamous cell carcinoma (ESCC) ranks among the top six deadliest malignancies globally, characterized by an alarmingly low five-year survival rate. This aggressive cancer is especially prevalent in Asian countries, where it is strongly influenced by various factors, including dietary habits. Organoids, a novel bioresource that are three-dimensional, miniature organ-like structures derived from stem cells or cancer cells in a laboratory, closely mimics the architecture and function of actual organs, providing an enhanced model for <em>in vivo</em> disease representation. These structures hold immense promise for advancing disease modelling, drug testing, personalized medicine, and investigating intricate biological processes. Nevertheless, numerous challenges remain, warranting further investigation. This review offers insights into the superiority of organoids in ESCC disease modelling, especially in drug screening and treatment optimization. The combination of organoids with gene editing will elucidate mechanisms of ESCC, which will be helpful for early molecular marker discovery and immunotherapy, providing potential strategies for therapeutic targets and personalized intervention.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101680"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614910","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":"A patient with Alagille syndrome had a novel JAG1 gene mutation","authors":"Ziting Peng,&nbsp;Yao Chen,&nbsp;Li Zhang,&nbsp;Tongdong Shi,&nbsp;Na Wang","doi":"10.1016/j.gendis.2025.101759","DOIUrl":"10.1016/j.gendis.2025.101759","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101759"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680818","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":"TTC21B variants disrupt the left-right asymmetry and pronephric development in zebrafish","authors":"Linxia Deng ,&nbsp;Yuan Yang ,&nbsp;Xiaoling Yin ,&nbsp;Jing Yang ,&nbsp;Yijie Duan ,&nbsp;Kang Wang ,&nbsp;Weicheng Duan ,&nbsp;Yu Zhang ,&nbsp;Bo Xiong ,&nbsp;Jianhua Zhou","doi":"10.1016/j.gendis.2025.101709","DOIUrl":"10.1016/j.gendis.2025.101709","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101709"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419781","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":"A comprehensive analysis of immune checkpoint receptor–ligand pairs in aortic diseases highlights the immunosuppressive roles of CD155 and CD274","authors":"Ying Shao ,&nbsp;Fatma Saaoud ,&nbsp;Keman Xu ,&nbsp;Yifan Lu ,&nbsp;Sheng Wu ,&nbsp;Laisel Martinez ,&nbsp;Roberto Vazquez-Padron ,&nbsp;Beata Kosmider ,&nbsp;Hong Wang ,&nbsp;Xiaofeng Yang","doi":"10.1016/j.gendis.2025.101724","DOIUrl":"10.1016/j.gendis.2025.101724","url":null,"abstract":"","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101724"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419792","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}