Genes & Diseases最新文献

英文中文

Blockage of SUMO E1 enzyme inhibits ocular lens fibrosis by mediating SMAD4 SUMOylation SUMO E1酶阻断通过介导SMAD4 SUMO酰化抑制晶状体纤维化。

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-08-28 DOI: 10.1016/j.gendis.2025.101827

Min Hou , Yujie Ding , Xuan Bao , Liangping Liu , Yulan Wang , Mingxing Wu

The ocular lens serves as an exemplary biological model for investigating mechanisms of fibrotic disease, particularly through its well-characterized epithelial–mesenchymal transition (EMT) process. In lens capsular fibrosis, lens epithelial cells (LECs) undergo phenotypic transformation mediated by the dysregulation of a complex signaling network. While multiple interconnected pathways have been implicated in this pathogenic process, current therapeutic strategies for anterior subcapsular cataract and postoperative capsular opacification remain predominantly surgical, underscoring the urgent need for targeted pharmacological interventions. SUMOylation, an essential post-translational modification system, orchestrates critical cellular processes, including gene expression, genome integrity, and cell cycle progression. Emerging evidence positions SUMOylation as a critical regulator of EMT in both fibrotic disorders and oncogenesis. Building on these insights, we hypothesized that SUMO-mediated post-transitional modifications may drive LEC transdifferentiation in lens fibrotic pathologies. Our experimental findings demonstrated that elevated global SUMOylation (SUMO1/2/3 conjugates) in human anterior subcapsular cataract specimens correlated with fibrotic progression. Sole SUMO isoform deficiency partially mitigated TGFβ₂-driven EMT and injury-induced anterior subcapsular cataract. SUMO E1 overexpression enhanced LEC proliferative capacity, migration potential, and EMT progression. Pharmacological SUMO E1 inhibition (ML792) suppressed TGFβ₂-induced SMAD4 SUMOylation, nuclear translocation, a critical TGFβ/SMAD signaling event. ML792 also eliminated TGFβ₂-induced LEC EMT and experimental anterior subcapsular cataract. Our results establish SMAD4 SUMOylation as a pivotal molecular switch in lens fibrosis pathogenesis. Employing inhibitory drugs of SUMO conjugation in the years to come has the potential to be a novel therapeutic strategy for fibrotic cataracts.

晶状体是研究纤维化疾病机制的典型生物学模型，特别是通过其具有良好特征的上皮-间质转化（EMT）过程。在晶状体囊纤维化中，晶状体上皮细胞（LECs）经历由复杂信号网络失调介导的表型转化。虽然这一致病过程涉及多种相互关联的途径，但目前对前囊下白内障和术后囊混浊的治疗策略仍以手术为主，因此迫切需要有针对性的药物干预。SUMOylation是一个重要的翻译后修饰系统，它协调了关键的细胞过程，包括基因表达、基因组完整性和细胞周期进程。新出现的证据表明，sumo酰化在纤维化疾病和肿瘤发生中都是EMT的关键调节因子。基于这些见解，我们假设sumo介导的过渡后修饰可能驱动晶状体纤维化病理中的LEC转分化。我们的实验结果表明，人类前囊下白内障标本中sumo酰化（sumo /2/3共轭物）的升高与纤维化进展相关。脚底SUMO异构体缺乏部分减轻tgf β2驱动的EMT和损伤性前囊下白内障。SUMO E1过表达增强LEC增殖能力、迁移潜力和EMT进展。药理SUMO E1抑制（ML792）抑制TGFβ2诱导的SMAD4 SUMOylation，核易位，一个关键的TGFβ/SMAD信号事件。ML792还能消除tgf β2诱导的LEC EMT和实验性前囊下白内障。我们的研究结果证实SMAD4 SUMOylation是晶状体纤维化发病机制中的关键分子开关。在未来的几年里，使用抑制SUMO结合的药物有可能成为纤维化白内障的一种新的治疗策略。

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引用次数: 0

TNFAIP8/TIPE2 inactivation modulates extracellular matrix organization gene expression and preserves the intervertebral disc structure in mice TNFAIP8/TIPE2失活可调节细胞外基质组织基因的表达，保留小鼠椎间盘结构

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-08-30 DOI: 10.1016/j.gendis.2025.101835

Zuozhen Tian , Ken Chen , Frances S. Shofer , Srish S. Chenna , Daniel Z. Sandroni , Ling Qin , Yejia Zhang

引用次数: 0

The molecular and immune landscape of the forkhead-box gene family in different subtypes of breast cancer 叉头盒基因家族在不同亚型乳腺癌中的分子和免疫景观

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-10-29 DOI: 10.1016/j.gendis.2025.101911

Xiaoman Bi , Liyang Chen , Deng Wu , Dahua Xu , Dehua Zheng , Zhizhou Xu , Zhenling Wan , Shaoping Zheng , Kongning Li , Shaojiang Zheng

引用次数: 0

Machine learning-based stratification of Parkinson’s disease progression using dysautonomia symptoms and transcriptomic signatures 基于机器学习的帕金森病进展分层，使用自主神经异常症状和转录组特征

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-08-22 DOI: 10.1016/j.gendis.2025.101831

Su-Jin Baek , Hyeong Joon Jun , Jae Hyeok Han , SeoHyun Lee , HuiYan Zhao , Muhammad Umar , Jae Young Jang , Jung-Hee Jang

引用次数: 0

CBS promotes tumor immune evasion by reducing MHC-I stability CBS通过降低MHC-I的稳定性促进肿瘤免疫逃避

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-07-25 DOI: 10.1016/j.gendis.2025.101782

Yanrong Yang , Yadong Guo , Shiyu Mao , Chengyuan Dong , Zhu Yu , Xudong Yao , Bing Shen

引用次数: 0

HSP90B1 facilitates glioma radiotherapy resistance by regulating RhoC ubiquitin‒proteasome degradation HSP90B1通过调节RhoC泛素蛋白酶体降解促进胶质瘤放疗抵抗

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-07-01 DOI: 10.1016/j.gendis.2025.101756

Jiacheng Xu , Yuduo Guo , Jingjing Yang , Guanjie Shang , Weihai Ning , Deshan Liu , Hongwei Zhang , Yongmei Song

Gliomas are primary brain tumors known for their resistance to radiotherapy and frequent recurrence. This might result from the high heterogeneity and transcriptional plasticity of gliomas. Heat shock proteins are associated with unfavorable tumor outcomes and protect tumors from the effects of radiotherapy. However, their influence on brain tumors is not fully understood. Initial analyses of glioma patients from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases who had undergone radiotherapy identified HSP90B1 as a crucial gene affecting patient prognosis. Subsequent investigations revealed that HSP90B1 enhanced the proliferation, migration, and invasion of glioma cells. It was also found to protect glioma cells from radiotherapy-induced apoptosis. Co-immunoprecipitation (CO-IP) found that HSP90B1 directly interacted with RhoC and protected it from degradation via the ubiquitin–proteasome pathway. Rescue experiments indicated that HSP90B1 might facilitate glioma migration, invasion, and radiotherapy resistance by modulating RhoC expression. A mouse model further demonstrated that gliomas expressing high levels of HSP90B1 exhibited decreased sensitivity to radiotherapy. Overall, our research revealed that HSP90B1 significantly impacts the prognosis of glioma patients treated with radiotherapy. Additionally, HSP90B1 might enhance glioma metastasis and resistance to radiotherapy by regulating RhoC expression. This regulatory effect was achieved by the directly binding of HSP90B1 to RhoC, thereby preventing its degradation through the ubiquitin–proteasome pathway.

胶质瘤是一种原发性脑肿瘤，以其对放射治疗的抵抗和频繁复发而闻名。这可能是由于胶质瘤的高度异质性和转录可塑性。热休克蛋白与不利的肿瘤预后有关，并保护肿瘤免受放射治疗的影响。然而，它们对脑肿瘤的影响尚不完全清楚。对肿瘤基因组图谱（TCGA）和中国胶质瘤基因组图谱（CGGA）数据库中接受放疗的胶质瘤患者的初步分析发现，HSP90B1是影响患者预后的关键基因。随后的研究表明，HSP90B1增强了胶质瘤细胞的增殖、迁移和侵袭。它还被发现可以保护胶质瘤细胞免受放射治疗诱导的细胞凋亡。共免疫沉淀（CO-IP）发现HSP90B1直接与RhoC相互作用，并通过泛素-蛋白酶体途径保护RhoC不被降解。救援实验表明，HSP90B1可能通过调节RhoC的表达促进胶质瘤的迁移、侵袭和放疗抵抗。小鼠模型进一步表明，表达高水平HSP90B1的胶质瘤对放疗的敏感性降低。总之，我们的研究显示HSP90B1显著影响胶质瘤放疗患者的预后。此外，HSP90B1可能通过调节RhoC的表达来促进胶质瘤的转移和对放疗的抵抗。这种调节作用是通过HSP90B1直接与RhoC结合，从而通过泛素-蛋白酶体途径阻止其降解而实现的。

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引用次数: 0

Pan-cancer analysis of ALK mutation and its association with tumor immunogenicity and the efficacy of immune checkpoint blockade 泛癌分析ALK突变及其与肿瘤免疫原性和免疫检查点阻断疗效的关系

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-05-28 DOI: 10.1016/j.gendis.2025.101701

Zhiyang Huang , Jiajun Chen , Yan Huang , Hong Zhao , Bin Zhao

Anaplastic lymphoma kinase (ALK) plays important roles in tumorigenesis and is involved in tumor immunogenicity through various pathways. Here, we conducted a comprehensive bioinformatic and clinical analysis on the characteristics of pan-cancer ALK mutation and its association with tumor immunity and the efficacy of immune checkpoint blockade. In 2930 patients with 11 tumor types treated with immune checkpoint inhibitors, the mutation of ALK indicated favorable overall survival (hazard ratio = 0.69; 95% confidence interval, 0.57–0.83; p < 0.001). We further developed and validated a nomogram to estimate the 12-month and 24-month survival probabilities after the initiation of immunotherapy. Moreover, multi-omics analysis on both intrinsic and extrinsic immune landscapes revealed that the mutation of ALK could enrich infiltration of immune cells, enhance tumor immunogenicity, and improve immune responses. In conclusion, ALK mutation is associated with promoted cancer immunity and can be treated as a biomarker for favorable outcomes in pan-cancer immune checkpoint blockade. These results have implications for treatment decision-making and developing immunotherapy for personalized care.

间变性淋巴瘤激酶（ALK）在肿瘤发生中起重要作用，并通过多种途径参与肿瘤的免疫原性。在此，我们对泛癌ALK突变的特征及其与肿瘤免疫的关系以及免疫检查点阻断的疗效进行了全面的生物信息学和临床分析。在接受免疫检查点抑制剂治疗的11种肿瘤类型的2930例患者中，ALK突变表明总体生存期有利（风险比= 0.69；95%可信区间为0.57-0.83;p < 0.001）。我们进一步开发并验证了一种nomogram来估计免疫治疗开始后12个月和24个月的生存概率。此外，对内、外源免疫景观的多组学分析显示，ALK突变可丰富免疫细胞浸润，增强肿瘤免疫原性，改善免疫应答。总之，ALK突变与促进癌症免疫有关，可以作为泛癌症免疫检查点阻断有利结果的生物标志物。这些结果对治疗决策和开发个性化护理的免疫疗法具有启示意义。

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引用次数: 0

Role of miR-101a in targeting Cox-2 to attenuate chondrocyte hypertrophic differentiation and osteoarthritis progression miR-101a在靶向Cox-2减轻软骨细胞肥厚分化和骨关节炎进展中的作用。

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-09-01 DOI: 10.1016/j.gendis.2025.101839

Rui Mi , Jinnan Chen , Tianxiang Zhu , Huiqin Bian , Rong Wei , Rushuang Deng , Tiaotiao Han , Qian Wang , Yaojuan Lu , Longwei Qiao , Yuting Liang , Qiping Zheng

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally, often playing critical roles in various biological processes. Recent studies have highlighted the involvement of miRNAs in chondrogenesis by targeting key marker genes. Among these, miR-101a has been identified as a significant regulator, previously reported to target cyclooxygenase-2 (Cox-2, ptgs2) in various contexts. Here, we investigate the role of miR-101a in chondrocyte hypertrophy and osteoarthritis (OA) progression, focusing on its regulation of Col10a1 expression. Using multiple web-based tools (TargetScan, PicTar, miRDB, and miRCODE), we identified miR-101a as a potential regulator of Col10a1. Our in vitro experiments demonstrated that miR-101a was down-regulated during chondrocyte hypertrophy in MCT and ATDC5 cells, while Col10a1 and Cox-2 expression levels were up-regulated. Overexpression of miR-101a via mimics resulted in a significant decrease in Col10a1 and Cox-2 at both mRNA and protein levels, whereas inhibition of miR-101a led to their up-regulation. Additionally, MMP-13 protein levels were reduced upon miR-101a overexpression, with no significant changes in Sox9 and Runx2 expression. Luciferase reporter assays confirmed that Cox-2 was a direct target of miR-101a, suggesting that miR-101a indirectly regulates Col10a1 expression via Cox-2. In vivo, intra-articular injection of miR-101a mimics in a medial meniscus-induced OA mouse model resulted in decreased Col10a1 expression and reduced articular damage, supporting the protective role of miR-101a in OA progression. Our findings highlight miR-101a as a negative regulator of chondrocyte hypertrophy through Cox-2, and could be a potential target for further exploration in OA therapy.

MicroRNAs （miRNAs）是一种小的非编码rna，在转录后调节基因表达，通常在各种生物过程中发挥关键作用。最近的研究强调了mirna通过靶向关键标记基因参与软骨形成。其中，miR-101a已被确定为一个重要的调节因子，先前报道在各种情况下靶向环氧化酶-2 （Cox-2, ptgs2）。在这里，我们研究了miR-101a在软骨细胞肥大和骨关节炎（OA）进展中的作用，重点研究了其对Col10a1表达的调节。使用多种基于网络的工具（TargetScan、PicTar、miRDB和miRCODE），我们确定miR-101a是Col10a1的潜在调节因子。我们的体外实验表明，miR-101a在MCT和ATDC5细胞的软骨细胞肥大过程中下调，而Col10a1和Cox-2的表达水平上调。通过模拟物过表达miR-101a导致Col10a1和Cox-2 mRNA和蛋白水平显著降低，而抑制miR-101a导致其上调。此外，miR-101a过表达后，MMP-13蛋白水平降低，而Sox9和Runx2的表达无显著变化。荧光素酶报告基因检测证实Cox-2是miR-101a的直接靶点，提示miR-101a通过Cox-2间接调控Col10a1的表达。在体内，在内侧半月板诱导的OA小鼠模型中，关节内注射miR-101a模拟物导致Col10a1表达降低，关节损伤减轻，支持miR-101a在OA进展中的保护作用。我们的研究结果强调miR-101a通过Cox-2作为软骨细胞肥大的负调节因子，可能是OA治疗中进一步探索的潜在靶点。

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引用次数: 0

Molecular characterization of a new R1925X point mutation mouse model for dysferlinopathy 一种新的R1925X点突变小鼠异ferlin病模型的分子特征

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-10-20 DOI: 10.1016/j.gendis.2025.101885

Camille Bouchard , Louis Despax , Joël Rousseau , Jacques P. Tremblay

引用次数: 0

MSC-EVs alleviate osteoarthritic joint pain and degeneration by suppressing IL-1β/NGF signaling msc - ev通过抑制IL-1β/NGF信号通路减轻骨关节炎关节疼痛和退行性变

IF 9.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & Diseases

Pub Date : 2026-05-01 Epub Date: 2025-12-11 DOI: 10.1016/j.gendis.2025.101981

Kristeen Ye Wen Teo , Chengming Wen , Raymond Chung Wen Wong , Wei Seong Toh

引用次数: 0

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全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

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Genes & Diseases

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