Genes & Diseases最新文献_第6页

Dermal T cell immunity and key regulatory signaling pathways: Implications in immune-mediated alopecia and hair regeneration 真皮T细胞免疫和关键调控信号通路：免疫介导的脱发和头发再生的意义

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-08 DOI: 10.1016/j.gendis.2025.101518

Nana Tao , Qingru Sun , Yuyuan Ying , Yitao Wang , Jianli Gao

引用次数: 0

Restriction of YWHAB-mediated YAP cytoplasmic retention is a novel mechanism underlying stemness maintenance and chemoresistance in ovarian cancer peritoneal metastasis 限制ywhab介导的YAP细胞质保留是卵巢癌腹膜转移中干细胞维持和化疗耐药的新机制

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-08 DOI: 10.1016/j.gendis.2025.101519

Chang Liu , Lei Shi , Zijun Meng , Manlin Zhang , Zhiqi Zhang , Yunzhe Li , Kaiwen Du , Muyao Yang , Lin Qiu , Jing Feng , Yuchen He , Jiayun Liu , Hua Zhang , Hongbin Zhang , Tingyuan Lang , Zhuo Yang

{"title":"Restriction of YWHAB-mediated YAP cytoplasmic retention is a novel mechanism underlying stemness maintenance and chemoresistance in ovarian cancer peritoneal metastasis","authors":"Chang Liu , Lei Shi , Zijun Meng , Manlin Zhang , Zhiqi Zhang , Yunzhe Li , Kaiwen Du , Muyao Yang , Lin Qiu , Jing Feng , Yuchen He , Jiayun Liu , Hua Zhang , Hongbin Zhang , Tingyuan Lang , Zhuo Yang","doi":"10.1016/j.gendis.2025.101519","DOIUrl":"10.1016/j.gendis.2025.101519","url":null,"abstract":"<div><div>Ovarian cancer (OC) peritoneal metastasis (OCPM) is a major cause of high mortality of OC, in which cancer cells incubated in ascites evolve various mechanisms to survive. Hippo/YAP singling plays multiple roles in carcinogenesis, however, its roles in OCPM have remained elusive. Here, we report that restriction of YWHAB-mediated YAP cytoplasmic retention is a critical mechanism underlying OCPM stemness maintenance. Combined tandem mass tag- and tissue microarray-based proteomic studies revealed YWHAB down-regulation in post-neoadjuvant chemotherapy OCPM tissues, which was confirmed in no-neoadjuvant-chemotherapy-response tissues, isolated OCPM stem cells, and induced cisplatin-resistant cells. Knockdown of YWHAB promoted stemness and resistance in parental complete or near-complete primary OCPM and OVCAR3 cells <em>in vitro</em> and <em>in vivo</em>. Mechanistic study showed that YWHAB directly bound to YAP and promoted YAP cytoplasmic retention and thus YWHAB restriction promoted YAP activity and stemness in OCPM in the cells in which the Hippo/YAP signaling was constitutively activated by overloaded constitutively active YAP (YAP5SA), and the effect of YWHAB knockdown was significantly abolished. The SH3 binding domain in YAP is critical for YWHAB-YAP binding. Alteration in the 5mc methylation level in the YWHAB promoter was observed in OCPM stem cells. In summary, our results reveal that restriction of YWHAB-mediated YAP cytoplasmic retention is a critical mechanism underlying OCPM stemness maintenance. Our findings suggest that YAP would be a therapeutic target for suppressing OCPM stemness caused by YWHAB restriction.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101519"},"PeriodicalIF":6.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331136","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

NADK tetramer defective mutants affect lung cancer response to chemotherapy via controlling NADK activity NADK四聚体缺陷突变体通过控制NADK活性影响肺癌对化疗的反应

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-07 DOI: 10.1016/j.gendis.2024.101510

Mengxue Hu , Fuxing Wang , Yue Zhu , Yi Yao , Huadong Pei , Zheng Liu , Pingfeng Zhang

{"title":"NADK tetramer defective mutants affect lung cancer response to chemotherapy via controlling NADK activity","authors":"Mengxue Hu , Fuxing Wang , Yue Zhu , Yi Yao , Huadong Pei , Zheng Liu , Pingfeng Zhang","doi":"10.1016/j.gendis.2024.101510","DOIUrl":"10.1016/j.gendis.2024.101510","url":null,"abstract":"<div><div>Nicotinamide adenine dinucleotide (NAD<sup>+</sup>) kinase (NADK) phosphorylates NAD<sup>+</sup> to generate NADP<sup>+</sup>, which plays a crucial role in maintaining NAD<sup>+</sup>/NADP<sup>+</sup> homeostasis, cellular redox balance, and metabolism. However, how human NADK activity is regulated, and how dysregulation or mutation of NADK is linked to human diseases, such as cancers, are still not fully understood. Here, we present a cryo-EM structure of human tetrameric NADK and elaborate on the necessity of the NADK tetramer for its activity. The N-terminal region of human NADK, which does not exist in bacterial NADKs, modulates tetramer conformation, thereby regulating its activity. A methylation-deficient mutant, R45H, within the N-terminal region results in increased NADK activity and confers cancer chemotherapy resistance. Conversely, mutations in NADK identified among cancer patients alter the tetramer conformation, resulting in NADK inactivation and increasing the sensitivity of lung cancer cells to chemotherapy. Our findings partially unveil the structural basis for NADK regulation, offering insights into the cancer etiology of patients carrying NADK mutations.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 4","pages":"Article 101510"},"PeriodicalIF":6.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852196","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

Gene-based safety evaluation of molybdenum-containing biomaterials for cardiovascular and cerebrovascular diseases 含钼生物材料治疗心脑血管疾病的基因安全性评价

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-05 DOI: 10.1016/j.gendis.2025.101516

Yang Zhang , Yunong Shen , Miaowen Jiang , Guiyou Liu , Hongkang Zhang , Baoying Song , Yufeng Zheng , Xunming Ji , Ming Li

引用次数: 0

Ribosome biogenesis: A central player in liver diseases 核糖体生物发生：肝脏疾病的中心角色

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-04 DOI: 10.1016/j.gendis.2025.101512

Wei Luo , Jing Zhou , Yongmin Yan , Xuezhong Xu

{"title":"Ribosome biogenesis: A central player in liver diseases","authors":"Wei Luo , Jing Zhou , Yongmin Yan , Xuezhong Xu","doi":"10.1016/j.gendis.2025.101512","DOIUrl":"10.1016/j.gendis.2025.101512","url":null,"abstract":"<div><div>Ribosome biogenesis is a multi-step process that initiates within the nucleolus, terminates in the cytoplasm, and determines the rate of protein synthesis. Ribosome biogenesis is essential for maintaining liver function. In eukaryotes, it involves producing and assembling approximately 200 factors and 80 ribosomal proteins. Mutations in ribosome proteins, ribosomal RNA processing, and ribosome assembly factors in the liver can result in liver disease. Hepatitis C virus causes acute or chronic infection and liver disease, which can progress to liver cirrhosis, cancer, and death. This review provides an overview of the effects of ribosomal biogenesis, including ribosomal RNA, ribosomal proteins, and ribosome biogenesis factors, on liver regeneration, hepatitis C virus, nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, and liver cancer. It lists drugs that exploit ribosome biogenesis to treat liver cancer. Targeting ribosome biogenesis shows promise as a therapeutic approach. A better understanding of this process will contribute to developing effective and targeted therapeutic strategies for ribosome biogenesis disorders.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101512"},"PeriodicalIF":6.9,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205047","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

circFOXO3 facilitated endothelial cell senescence and atherosclerosis through binding to HnRNPK circFOXO3通过与HnRNPK结合促进内皮细胞衰老和动脉粥样硬化

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-04 DOI: 10.1016/j.gendis.2025.101517

Jing-yu Wu , Yu-lan Zhou , Shui-hong Lu , Zhi-peng Yang , Zhao-fu Liao , Dong-liang Liu , Hai-liang Mo , Yi-tuan Xie , Xinguang Liu , Xing-dong Xiong

引用次数: 0

Identification of a tertiary lymphoid structure (TLS)-related signature for ovarian cancer prognosis suggests a potential role of STAT5A in TLS maturation 鉴别出与卵巢癌预后相关的三级淋巴样结构（TLS）特征，提示STAT5A在TLS成熟中的潜在作用

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-04 DOI: 10.1016/j.gendis.2025.101514

Jiani Yang , Yue Zhang , Shanshan Cheng , Yanna Xu , Meixuan Wu , Sijia Gu , Mingjun Ma , Yaqian Zhao , Chao Wang , Yu Wang

引用次数: 0

Identification of a splice site mutation in IL2RG in a Chinese boy with X-linked severe combined immunodeficiency 中国一名x连锁严重联合免疫缺陷男孩IL2RG剪接位点突变的鉴定

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-04 DOI: 10.1016/j.gendis.2025.101515

Feng Ding , He Zhang , Xiangxiang Liu , Lin Lei , Hongyi Zhang , Zhichao Liu , Mutong Fang , Shuihua Lu

引用次数: 0

TET1: The epigenetic architect of clinical disease progression TET1：临床疾病进展的表观遗传学架构师

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-04 DOI: 10.1016/j.gendis.2025.101513

Keyvan Jabbari , Ali Khalafizadeh , Mahboubeh Sheikhbahaei , Hossein Soltaninejad , Sadegh Babashah

{"title":"TET1: The epigenetic architect of clinical disease progression","authors":"Keyvan Jabbari , Ali Khalafizadeh , Mahboubeh Sheikhbahaei , Hossein Soltaninejad , Sadegh Babashah","doi":"10.1016/j.gendis.2025.101513","DOIUrl":"10.1016/j.gendis.2025.101513","url":null,"abstract":"<div><div>The ten-eleven translocation 1 (TET1) protein, a member of the human α-ketoglutarate-dependent dioxygenase TET family, functions as a 5-methylcytosine hydroxylase with a strong affinity for genomic regions enriched with 5′-CpG-3′ dinucleotides, particularly CpG islands. TET1 is critical in initiating DNA demethylation and maintaining a balanced interaction between demethylation and DNA methylation, which is essential for genomic methylation stability and precise epigenetic regulation. By removing methyl groups from specific tumor suppressor genes, TET1 can influence their expression. This review summarizes the latest advancements in TET1 research, emphasizing its role in demethylation mechanisms and its significance in regulatory processes related to clinical conditions. TET1 is a crucial mediator of demethylation, although the precise details of this mechanism are not yet fully understood. Additionally, TET1 plays a key role in inhibiting tumor progression, but its effects vary across different tumors. This variability arises from its interactions with diverse signaling pathways, where it can function either as an antagonist or a promoter. The role of TET1 remains controversial in certain cancer types, and its potential oncogenic functions have attracted growing interest, opening new avenues for investigation.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 5","pages":"Article 101513"},"PeriodicalIF":6.9,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205048","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

Integrated multi-omics characterization of neuroblastoma with bone or bone marrow metastasis 神经母细胞瘤骨转移或骨髓转移的多组学综合表征

IF 6.9 2区医学

Genes & Diseases Pub Date : 2025-01-03 DOI: 10.1016/j.gendis.2024.101511

Kai Huang , Linyu Yang , Yue Ma, Lijian Cao, Suwen Li, Zhenzhen Zhao, Jianwu Zhou, Shan Wang

{"title":"Integrated multi-omics characterization of neuroblastoma with bone or bone marrow metastasis","authors":"Kai Huang , Linyu Yang , Yue Ma, Lijian Cao, Suwen Li, Zhenzhen Zhao, Jianwu Zhou, Shan Wang","doi":"10.1016/j.gendis.2024.101511","DOIUrl":"10.1016/j.gendis.2024.101511","url":null,"abstract":"<div><div>The pathogenesis of neuroblastoma with bone or bone marrow metastasis (NB-BBM) and its complex immune microenvironment remain poorly elucidated, hampering the advancement of effective risk prediction for BBM and limiting therapeutic strategies. Feature recognition of 142 paraffin-embedded hematoxylin-eosin-stained tumor section images was conducted using a Swin-Transformer for pathological histology to predict NB-BBM occurrence. Single-cell transcriptomics identified a tumor cell subpopulation (NB3) and two tumor-associated macrophage (TAM) subpopulations (SPP1<sup>+</sup> TAMs and IGHM<sup>+</sup> TAMs) closely associated with BBM and highlighted transketolase (TKT) as a key molecular marker for metastatic progression in NB. This extensive multi-omics investigation into NB-BBM enhances our understanding of single-cell transcriptional dynamics in NB beyond existing research, outlining the evolution from <em>in situ</em> carcinoma through tumorigenesis to bone marrow metastases. Furthermore, exploration of the immune microenvironment identified specific subpopulations of TAMs crucial in promoting NB-BBM, presenting new avenues for immunotherapy. These insights enhance our understanding of the metastatic process from NB to BBM and facilitate the development of more effective diagnostic and therapeutic strategies for this aggressive pediatric cancer.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"12 3","pages":"Article 101511"},"PeriodicalIF":6.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0