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Exosomal IGFALS as a prognostic biomarker in hepatocellular Carcinoma: Associations with immune infiltration and clinical outcomes 外泌体IGFALS作为肝细胞癌的预后生物标志物:与免疫浸润和临床结果的关系
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-04-01 Epub Date: 2026-01-23 DOI: 10.1016/j.mcp.2026.102061
Longfei Fan , Zhaoying Wang , Tao Tao , Dongdong Huang , Xiaoyun Tang , Rui Wang , Zhongqiang Qin , Bo Xie , Yi Tan

Purpose

This investigation seeks to examine the relationship between exosomal Insulin-like Growth Factor Binding Protein Acid Labile Subunit (IGFALS) gene expression, immune infiltration, and clinical outcomes in individuals with hepatocellular carcinoma (HCC).

Method

Clinical data and IGFALS expression levels were obtained from the TCGA and GEO databases. Immunohistochemistry was performed to confirm IGFALS expression in both HCC and adjacent non-tumor tissues. To validate survival analyses, restricted cubic spline models were used to explore associations between overall survival (OS) and the expression of IGFALS in liver hepatocellular carcinoma (LIHC). Gene set enrichment analysis (GSEA) identified IGFALS-associated pathways, while Gene set enrichment analysis (ssGSEA) evaluated IGFALS-immune cell infiltration correlations. Functional characterization included proliferation, migration/invasion, molecular profiling, and apoptosis assays.

Result

Compared to normal tissues, IGFALS expression levels were notably decreased in tumor tissues. A notable link was detected between IGFALS expression and multiple clinical factors, including gender, weight, residual tumor, adjacent hepatic tissue inflammation, vascular invasion, AFP, BCLC, tumor size, multinodular, TACE, and satellite lesion in HCC. Reduced IGFALS expression in HCC was correlated with decreased OS. Moreover, the IGFALS level in malignant tumor cells post-immunotherapy was observed to be markedly higher than that in the pre-treatment phase. A strong association between IGFALS and immune infiltration levels was also established. At the same time, in vitro experiments also verified the function of the IGFALS gene.

Conclusion

The exosomal IGFALS gene holds potential as a prospective indicator for assessing the outcome of individuals with HCC.
目的:本研究旨在探讨肝细胞癌(HCC)患者外泌体胰岛素样生长因子结合蛋白酸不稳定亚基(IGFALS)基因表达、免疫浸润和临床结局之间的关系。方法:从TCGA和GEO数据库中获取临床资料和IGFALS表达水平。免疫组织化学证实IGFALS在HCC和邻近非肿瘤组织中的表达。为了验证生存分析,我们使用限制三次样条模型来探讨肝细胞癌(LIHC)中总生存期(OS)与IGFALS表达之间的关系。基因集富集分析(GSEA)鉴定了igfals相关途径,而基因集富集分析(ssGSEA)评估了igfals与免疫细胞浸润的相关性。功能表征包括增殖、迁移/侵袭、分子分析和凋亡分析。结果:与正常组织相比,IGFALS在肿瘤组织中的表达水平明显降低。在HCC中,IGFALS的表达与性别、体重、肿瘤残留、邻近肝组织炎症、血管浸润、AFP、BCLC、肿瘤大小、多结节、TACE、卫星病变等临床因素均有显著相关性。HCC中IGFALS表达降低与OS降低相关。此外,免疫治疗后恶性肿瘤细胞中的IGFALS水平明显高于治疗前。IGFALS与免疫浸润水平之间也存在密切联系。同时,体外实验也验证了IGFALS基因的功能。结论:外泌体IGFALS基因有潜力作为评估HCC患者预后的前瞻性指标。
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引用次数: 0
Emerging roles of artificial intelligence/machine learning (AI/ML) towards new understandings in molecular crosstalk between circRNA–CUL3–TKI to resensitize chemoresistant cancers 人工智能/机器学习(AI/ML)在circRNA-CUL3-TKI分子串扰中对化疗耐药癌症重敏的新认识中的新兴作用
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI: 10.1016/j.mcp.2026.102063
Pranjali Dutta, Samiksha Middya, Siddharth Shome, Manshi Kumari Gupta, Poobana Dharmalingam, C. Sudandiradoss
Cancer arises and is resistant to therapy via intricate molecular networks that are poorly characterised. While individually, Cullin-3 (CUL3) and circular RNAs (circRNAs) have been reported to modulate cancer, their synergistic effect in the modulation of tyrosine kinase inhibitor (TKI) resistance is yet to be studied. An emerging circRNA–CUL3–TKI regulatory framework is highlighted as a potential contributor to oncogenesis and drug sensitivity in this review. We discuss how circRNA-associated networks may influence CUL3-dependent pathways implicated in tumour resistance to therapy by modulating autophagy, ferroptosis, stress-responses, and redox signalling. Exosomal circRNAs and circRNAs of the CUL3 gene itself are highlighted as dynamic mediators of resistance as well as biomarkers. How they interact with Kelch-like ECH-associated protein 1- Nuclear factor erythroid 2-related factor 2 (KEAP1–NRF2) signalling reveals that they enhance tumour survival under therapy pressure. By highlighting key processes of carcinogenesis and resistance, the circRNA–CUL3–TKI axis represents a testable therapeutic framework. Modeling circRNA networks, predicting TKI response, finding biomarkers, and developing personalised treatment plans are all made possible by applications of artificial intelligence and machine learning (AI/ML), as explored in this review. Antisense oligonucleotides, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based molecules, neddylation inhibitors or PROteolysis TArgeting Chimera (PROTACs) are examples of potential interventions that, when combined with AI/ML techniques, improve therapeutic efficacy and may inform future desensitisation strategies. These collectively emphasize the emerging applications for AI/ML in understanding the circRNA–CUL3–TKI crosstalk and developing methods to resensitize cancers that are resistant to therapy.
癌症通过复杂的分子网络产生并对治疗产生抗药性,而这些分子网络的特征却很不明确。虽然culin -3 (CUL3)和环状rna (circRNAs)已被报道单独调节癌症,但它们在调节酪氨酸激酶抑制剂(TKI)耐药性方面的协同作用尚未被研究。在本综述中,一个新兴的circRNA-CUL3-TKI调控框架被强调为肿瘤发生和药物敏感性的潜在因素。我们讨论了circrna相关网络如何通过调节自噬、铁凋亡、应激反应和氧化还原信号传导来影响cul3依赖通路,cul3依赖通路与肿瘤耐药有关。外泌体环状rna和CUL3基因本身的环状rna被强调为耐药的动态介质和生物标志物。它们如何与kelch样ech相关蛋白1-核因子2-相关因子2 (KEAP1-NRF2)信号相互作用揭示了它们在治疗压力下提高肿瘤存活率。通过强调致癌和耐药的关键过程,circRNA-CUL3-TKI轴代表了一个可测试的治疗框架。本文探讨了人工智能和机器学习(AI/ML)的应用,使circRNA网络建模、预测TKI反应、寻找生物标志物和制定个性化治疗计划成为可能。反义寡核苷酸、基于CRISPR的簇化间隔短回文重复序列(Clustered Regularly Interspaced Short Palindromic Repeats,简称CRISPR)分子、类化修饰抑制剂或靶向嵌合体(PROteolysis TArgeting Chimera,简称PROTACs)是潜在干预措施的例子,当与AI/ML技术结合使用时,可以提高治疗效果,并可能为未来的脱敏策略提供信息。这些共同强调了AI/ML在理解circRNA-CUL3-TKI串扰和开发对治疗有抗性的癌症重新敏感的方法方面的新兴应用。
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引用次数: 0
Metformin and oncogenic pathways: Crosstalk between energy sensing and tumor progression 二甲双胍和致癌途径:能量感知和肿瘤进展之间的串扰。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-04-01 Epub Date: 2026-02-11 DOI: 10.1016/j.mcp.2026.102068
Ying Zhang, Long Zhao, Kai Zhang, Yuqiu Gao
Metformin, a widely prescribed oral biguanide for type 2 diabetes mellitus, has gained significant attention as a potential anti-cancer agent. Beyond its established role in improving insulin sensitivity and lowering blood glucose, preclinical and epidemiological studies suggest that metformin exerts anti-tumor effects through both insulin-dependent and insulin-independent mechanisms. Central to its activity is the activation of AMP-activated protein kinase (AMPK), which disrupts the mammalian target of rapamycin (mTOR) pathway, leading to cell cycle arrest, apoptosis, and reduced tumor growth. Additionally, metformin modulates oncogenic signaling networks such as PI3K/Akt, Erk, and receptor tyrosine kinases, while influencing tumor metabolism, angiogenesis, and immune responses. By inhibiting mitochondrial complex I, metformin interferes with cancer cell bioenergetics and the Warburg effect, further contributing to its anti-cancer potential. Clinical studies, however, have yielded mixed results, underscoring the complexity of metformin's effects and the need for rigorous investigation. This review highlights the multifaceted mechanisms by which metformin impacts tumor progression and discusses its promise and challenges as a therapeutic agent in cancer prevention and treatment.
二甲双胍是一种广泛用于治疗2型糖尿病的口服双胍类药物,作为一种潜在的抗癌药物受到了广泛的关注。临床前和流行病学研究表明,二甲双胍除了具有改善胰岛素敏感性和降低血糖的作用外,还通过胰岛素依赖和胰岛素非依赖两种机制发挥抗肿瘤作用。其活性的核心是amp活化蛋白激酶(AMPK)的激活,AMPK破坏哺乳动物雷帕霉素靶蛋白(mTOR)途径,导致细胞周期阻滞、细胞凋亡和肿瘤生长减少。此外,二甲双胍调节致癌信号网络,如PI3K/Akt、Erk和受体酪氨酸激酶,同时影响肿瘤代谢、血管生成和免疫反应。通过抑制线粒体复合体I,二甲双胍干扰癌细胞生物能量学和Warburg效应,进一步促进其抗癌潜力。然而,临床研究结果好坏参半,强调了二甲双胍作用的复杂性和严格研究的必要性。这篇综述强调了二甲双胍影响肿瘤进展的多方面机制,并讨论了其作为癌症预防和治疗药物的前景和挑战。
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引用次数: 0
The role of WNT10B expression in the prognosis of colorectal cancer: A retrospective study based on TCGA database and clinical data WNT10B表达在结直肠癌预后中的作用:基于TCGA数据库和临床资料的回顾性研究
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-04-01 Epub Date: 2026-01-26 DOI: 10.1016/j.mcp.2026.102062
Jie Shao , Xia Zheng , Lin Yang , Qian Yu , Zhichao Jin , Ran Yang , Zhanying Zhao , Borui Liu , Ruiping Wang , Mao Wang

Objective

To evaluate the prognostic value of WNT10B expression in colorectal cancer (CRC) for personalized management.

Methods

We analyzed a TCGA cohort of 644 CRC patients to assess differential expression of WNT family genes between 51 paired tumor-normal samples. Patients were stratified by WNT10B expression to compare overall survival (OS) and progression-free interval (PFI). Prognostic factors were identified via univariate and multivariate Cox regression. For validation, WNT10B protein expression was examined by immunohistochemistry in a separate cohort of 176 CRC patients who underwent surgery at our institution (2016–2020). Kaplan-Meier analysis and univariate Cox regression were used to correlate WNT10B levels with OS and disease-free survival (DFS).

Results

According to TCGA data, WNT10B was upregulated in CRC tumors. Elevated expression was correlated with reduced OS and PFI. Univariate analysis for OS implicated high WNT10B, age >65, lymph node/distant metastasis, positive margin, deep invasion, and abnormal CEA. For PFI, significant factors included high WNT10B, lymph node/distant metastasis, positive margin, deep invasion, and abnormal CEA. Multivariate analysis confirmed high WNT10B, age >65, and a positive margin as independent prognostic factors for OS. High WNT10B expression, distant metastasis, invasion depth and abnormal carcinoembryonic antigen level are the risk factors for independently predicting high tumor recurrence; Postoperative Kaplan-Meier analysis revealed that reduced WNT10B expression was associated with prolonged overall survival (OS), while disease-free survival (DFS) also tended to be longer in the low-expression group, although this trend did not reach statistical significance. Univariate Cox regression identified several factors adversely affecting OS, including elevated WNT10B expression, age ≥65 years, lymph node metastasis, distant metastasis, positive surgical margin, vascular invasion, and perineural invasion. Lymph node metastasis, distant metastasis, vascular invasion, and perineural invasion were also associated with increased recurrence risk. Multivariate analysis confirmed that age ≥65 years, distant metastasis, and vascular invasion were independent predictors of shorter OS. Distant metastasis emerged as an independent risk factor for tumor recurrence.

Conclusion

WNT10B is upregulated in colorectal cancer and correlates with unfavorable outcomes, suggesting its potential utility as a prognostic biomarker and therapeutic target.
目的:探讨WNT10B在结直肠癌(CRC)中的表达对个体化治疗的预后价值。方法:我们分析了644例CRC患者的TCGA队列,以评估51对肿瘤与正常样本之间WNT家族基因的差异表达。根据WNT10B表达对患者进行分层,比较总生存期(OS)和无进展间期(PFI)。通过单因素和多因素Cox回归确定预后因素。为了验证WNT10B蛋白的表达,我们通过免疫组织化学检测了在我院接受手术的176例结直肠癌患者的单独队列(2016-2020)。采用Kaplan-Meier分析和单变量Cox回归分析WNT10B水平与OS和无病生存期(DFS)的相关性。结果:TCGA数据显示,WNT10B在结直肠癌肿瘤中表达上调。表达升高与OS和PFI降低相关。OS的单因素分析涉及高WNT10B,年龄在65岁以下,淋巴结/远处转移,阳性边缘,深部浸润和异常CEA。PFI的显著因素包括高WNT10B、淋巴结/远处转移、边缘阳性、深部浸润和CEA异常。多因素分析证实,高WNT10B、年龄50 ~ 65岁和阳性边缘是OS的独立预后因素。WNT10B高表达、远处转移、浸润深度及癌胚抗原水平异常是独立预测肿瘤高复发的危险因素;术后Kaplan-Meier分析显示,WNT10B表达降低与总生存期(OS)延长相关,而低表达组的无病生存期(DFS)也趋于延长,但这一趋势未达到统计学意义。单因素Cox回归确定了影响OS的几个不利因素,包括WNT10B表达升高、年龄≥65岁、淋巴结转移、远处转移、手术切缘阳性、血管侵袭和神经周围侵袭。淋巴结转移、远处转移、血管浸润和神经周围浸润也与复发风险增加有关。多因素分析证实年龄≥65岁、远处转移和血管侵袭是较短OS的独立预测因素。远处转移成为肿瘤复发的独立危险因素。结论:WNT10B在结直肠癌中表达上调,并与不良预后相关,提示其作为预后生物标志物和治疗靶点的潜在用途。
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引用次数: 0
Stem cell-derived and plant-derived exosomes: Promising therapeutics for skin healing and regeneration 干细胞来源和植物来源的外泌体:皮肤愈合和再生的有希望的治疗方法。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-04-01 Epub Date: 2026-02-06 DOI: 10.1016/j.mcp.2026.102064
Xue Wang , Wenjun Wang , Ran Yao , Zhao Liu , Qianqing Wang
Stem cell-derived and plant-derived exosomes are emerging as promising therapeutic agents in cutaneous repair, regeneration, and rejuvenation. They facilitate wound healing and skin revitalization through multifaceted mechanisms, including immunomodulation, promotion of cellular differentiation, and stimulation of angiogenesis. Additionally, their ability to modulate collagen production and remodeling underscores their potential in addressing skin aging and improving cosmetic outcomes. Consequently, exosome-based therapies show promise for a range of conditions, from challenging wounds and skin aging to pigmentary disorders, hair loss, certain immune-mediated dermatoses. To ensure a comprehensive and unbiased synthesis of the current evidence, this systematic review was conducted following a structured methodology, encompassing a search across multiple major databases over a defined 20-year period. This review systematically outlines the roles and applications of commonly employed plant exosomes and stem cell exosomes in recent years' advancements in skin repair and cosmetic dermatology. By synthesizing the current understanding of their mechanisms and clinical potential, this review aims to highlight viable therapeutic strategies that bridge the gap between medical dermatology and aesthetic medicine.
干细胞来源的外泌体和植物来源的外泌体在皮肤修复、再生和年轻化方面正在成为有前途的治疗药物。它们通过多方面的机制促进伤口愈合和皮肤再生,包括免疫调节、促进细胞分化和刺激血管生成。此外,它们调节胶原蛋白生成和重塑的能力强调了它们在解决皮肤老化和改善美容效果方面的潜力。因此,基于外泌体的疗法显示出对一系列疾病的希望,从挑战性伤口和皮肤老化到色素紊乱、脱发、某些免疫介导的皮肤病。为了确保对现有证据进行全面和公正的综合,本系统评价采用结构化方法进行,包括在确定的20年期间对多个主要数据库进行搜索。本文系统地综述了近年来常用的植物外泌体和干细胞外泌体在皮肤修复和美容皮肤科中的作用和应用。通过综合目前对其机制和临床潜力的理解,本综述旨在突出可行的治疗策略,弥合医学皮肤科和美容医学之间的差距。
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引用次数: 0
Granulocyte-macrophage colony-stimulating factor at work: Promoting vascular maturation for accelerated wound healing. 粒细胞-巨噬细胞集落刺激因子的作用:促进血管成熟加速伤口愈合。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-03-13 DOI: 10.1016/j.mcp.2026.102069
Wenjie Ying, Shuangshuang Wang, Pengyu Sun, Jianhai Chen, Haijun Cai

Background: Wound healing is a complex biological process involving vascular remodeling and tissue repair. However, the mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates vascular maturation during wound healing remains unclear. This study aims to investigate the biological mechanism by which GM-CSF promotes vascular maturation and enhances wound repair.

Methods: Human dermal microvascular endothelial cells (ECs) and human brain vascular pericytes (PCs) were cultured separately or in co-culture and treated with various concentrations of GM-CSF. Cell proliferation and migration were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylformazan and Transwell assays. Tube formation assays were performed to evaluate angiogenic potential. The expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot. Endothelial permeability was analyzed using fluorescein isothiocyanate (FITC)-dextran staining. The expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) was assessed by immunofluorescence.

Results: GM-CSF substantially raised EC and PC proliferation and migration in a dose-dependent manner, with more pronounced effects observed in co-culture conditions. GM-CSF grew VEGF and Ang-1 in PCs and enhanced tube formation and barrier integrity in both mono- and co-cultured ECs. Furthermore, GM-CSF-stimulated PC-conditioned medium induced the upregulation of PECAM-1 in ECs.

Conclusion: GM-CSF promotes PECAM1 expression, angiogenesis, and vascular maturation in ECs by upregulating VEGF and Ang-1 in PCs. These effects enhance the interaction between endothelial cells and pericytes, thereby contributing to vascular stabilization and improved wound healing.

背景:伤口愈合是一个复杂的生物过程,涉及血管重塑和组织修复。然而,粒细胞-巨噬细胞集落刺激因子(GM-CSF)在伤口愈合过程中促进血管成熟的机制尚不清楚。本研究旨在探讨GM-CSF促进血管成熟和伤口修复的生物学机制。方法:分别培养人皮肤微血管内皮细胞(ECs)和人脑血管周细胞(PCs),并用不同浓度的GM-CSF处理。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基甲马赞和Transwell测定法评估细胞增殖和迁移。进行血管形成试验以评估血管生成潜力。采用酶联免疫吸附法(ELISA)和Western blot检测血管内皮生长因子(VEGF)和血管生成素-1 (Ang-1)的表达。采用异硫氰酸荧光素-葡聚糖染色法分析内皮细胞的通透性。免疫荧光法检测血小板内皮细胞粘附分子1 (PECAM-1)的表达。结果:GM-CSF显著提高EC和PC的增殖和迁移,且呈剂量依赖性,共培养条件下效果更明显。GM-CSF在pc中促进VEGF和Ang-1的生长,并在单个和共培养的ECs中增强管的形成和屏障的完整性。此外,gm - csf刺激的pc条件培养基诱导ECs中PECAM-1的上调。结论:GM-CSF通过上调pc中VEGF和Ang-1,促进ECs中PECAM1的表达、血管生成和血管成熟。这些作用增强了内皮细胞和周细胞之间的相互作用,从而有助于血管稳定和改善伤口愈合。
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引用次数: 0
Exosome-Mediated Neuroprotection in Vascular Dementia: Mechanisms, Molecular Pathways, and Therapeutic Prospects. 外泌体介导的血管性痴呆的神经保护:机制、分子途径和治疗前景。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-02-19 DOI: 10.1016/j.mcp.2026.102066
Farzaneh Fazli, Samin Davoody, Nicole Vissers, Sanaz Bordbar, Reza Rahbarghazi, Mohammad Karimipour, Hamid Taiefi Nasrabadi

Exosomes, a specialized class of extracellular vesicles, exhibit significant therapeutic potential for neurological disorders. In particular for vascular dementia (VaD), the second most common form of dementia. VaD is characterized by cognitive and behavioral impairments, often linked to hippocampal damage resulting from its vulnerable vascular structure, which disrupts memory formation and retrieval. Secreted by various cell types within the central nervous system, exosomes mediate intercellular communication by transporting bioactive molecules. Growing evidence indicates that exosomes enhance synaptic plasticity, modulate neuroinflammation, inhibit apoptosis, and promote angiogenesis, supporting their therapeutic potential in VaD. Given the urgent need for effective treatments and the unique ability of exosomes to cross the blood-brain barrier (BBB) and deliver multi-targeted therapies, research in this field is critically important. It offers a viable pathway toward the development of disease-modifying interventions for a condition that is currently managed primarily through symptomatic treatment. This review summarizes current knowledge on the function of exosomes in the central nervous system, examines recent advances in exosome-based strategies for VaD, and discusses ongoing challenges and future directions for their clinical translation.

外泌体是一类特殊的细胞外囊泡,对神经系统疾病具有重要的治疗潜力。特别是血管性痴呆(VaD),第二种最常见的痴呆形式。VaD的特点是认知和行为障碍,通常与海马损伤有关,海马损伤是由于其脆弱的血管结构,破坏了记忆的形成和检索。外泌体由中枢神经系统内各种类型的细胞分泌,通过运输生物活性分子介导细胞间通讯。越来越多的证据表明,外泌体增强突触可塑性,调节神经炎症,抑制细胞凋亡,促进血管生成,支持其治疗VaD的潜力。鉴于迫切需要有效的治疗方法,以及外泌体穿越血脑屏障(BBB)并提供多靶向治疗的独特能力,该领域的研究至关重要。它为目前主要通过对症治疗进行管理的疾病改善干预提供了一条可行的途径。本文综述了目前关于外泌体在中枢神经系统中的功能的知识,研究了基于外泌体的VaD治疗策略的最新进展,并讨论了其临床翻译的当前挑战和未来方向。
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引用次数: 0
Reveal the regulatory role of DDX10 in diffuse large B-cell lymphoma: binding with FBL to promote cell proliferation and invasion 揭示DDX10在弥漫性大b细胞淋巴瘤中的调节作用:与FBL结合促进细胞增殖和侵袭
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-02-01 Epub Date: 2025-12-01 DOI: 10.1016/j.mcp.2025.102057
Xin Chen, Weiqing Chen

Background

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous malignancy with an unidentified molecular etiology. This study aims to investigate the role of DEAD-box helicase 10 (DDX10), a novel carcinogenic gene, in DLBCL.

Methods

The expression of DDX10 in DLBCL was analyzed by the GEPIA2 bioinformatics tool. DDX10 and fibrillarin (FBL) expressions in DLBCL patients’ cancer tissues and cell lines were measured via quantitative real-time reverse transcription polymerase chain reaction. RNA immunoprecipitation assay was used to confirm FBL-DDX10 interaction. The effects of DDX10/FBL overexpression and knockdown on cell viability, invasion, and Wnt/β-catenin pathway proteins were evaluated in DLBCL cell lines.

Results

DDX10 and FBL exhibited elevated expression levels in patients with DLBCL, particularly in those with stage III or IV DLBCL. DDX10 can bind to FBL in DLBCL cells. Silencing of DDX10 or FBL suppressed viability, proliferation and invasion, and downregulated the expressions of β-catenin, cyclin D1, and c-Myc proteins in DLBCL cells. The regulatory impact of DDX10 or FBL silencing on DLBCL cells was counteracted by the overexpression of FBL or DDX10.

Conclusion

DDX10 contributes to the proliferation and invasion of DLBCL cells via positively regulating FBL, highlighting the DDX10–FBL axis as a potential therapeutic target. This work provides new insights into DLBCL pathogenesis and underscores the biomedical relevance of targeting DDX10–FBL.
背景:弥漫性大B细胞淋巴瘤(DLBCL)是一种分子病因不明的异质性恶性肿瘤。本研究旨在探讨一种新型致癌基因DEAD-box解旋酶10 (DDX10)在DLBCL中的作用。方法采用GEPIA2生物信息学工具分析DDX10在DLBCL中的表达。采用实时定量逆转录聚合酶链反应检测DLBCL患者肿瘤组织和细胞系中DDX10和纤原蛋白(FBL)的表达。RNA免疫沉淀法证实FBL-DDX10相互作用。研究了DDX10/FBL过表达和敲低对DLBCL细胞活力、侵袭性和Wnt/β-catenin通路蛋白的影响。结果ddx10和FBL在DLBCL患者中表达水平升高,特别是在III期或IV期DLBCL患者中。DDX10可与DLBCL细胞中的FBL结合。DDX10或FBL的沉默抑制了DLBCL细胞的活力、增殖和侵袭,下调了β-catenin、cyclin D1和c-Myc蛋白的表达。DDX10或FBL沉默对DLBCL细胞的调控作用被FBL或DDX10的过表达所抵消。结论ddx10通过正调控FBL参与DLBCL细胞的增殖和侵袭,提示DDX10-FBL轴可能是潜在的治疗靶点。这项工作为DLBCL的发病机制提供了新的见解,并强调了靶向DDX10-FBL的生物医学相关性。
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引用次数: 0
Corrigendum to “Establishment of CRISPR/Cas9 lineage tracking technology for pig embryos” [Molecular and Cellular Probes 83 (2025) 102046] “猪胚胎CRISPR/Cas9谱系追踪技术的建立”[Molecular and Cellular Probes 83(2025) 102046]的勘误表。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-02-01 Epub Date: 2025-09-13 DOI: 10.1016/j.mcp.2025.102050
Xiang-Qian Meng , Xue-Ling Xu , Yu Gao , Shou-Long Deng
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引用次数: 0
Identification of lymphangiogenesis-related diagnostic model for predicting abdominal aortic aneurysm onset and progression and validation of lymphopoiesis in abdominal aortic aneurysm 预测腹主动脉瘤发生发展的淋巴管生成相关诊断模型的建立及腹主动脉瘤淋巴生成的验证。
IF 3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-02-01 Epub Date: 2025-11-01 DOI: 10.1016/j.mcp.2025.102054
Su Qin , Jing Zhang , Meifang Cao , Tao Jiang , Baohong Jiang
This study aims to explore the lymphangiogenesis (LG)-related diagnostic markers of abdominal aortic aneurysm (AAA) through bioinformatics, as well as the alteration of the regional lymphatic system during the progression of AAA and the influence of lymphatic drainage obstruction on AAA progression. 2957 differentially expressed genes (DEGs) were identified between the AAA patient group and the healthy donor group in Gene Expression Omnibus microarray datasets. Subsequently, the DEGs and the LG gene were intersected, and 93 genes were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to obtain module genes. Module genes intersected with the above 93 genes, and 26 genes were obtained. Five hub genes (HSPA5, RAB10, RAB1A, RAF1, SMAD4) identified by machine learning may serve as diagnostic candidates for AAA patients through nomogram and ROC evaluation. Gene set enrichment analysis (GSEA) and immune infiltration analysis were performed further to understand the function of these candidate genes and explore the effect of immunity in AAA, respectively. By establishing an AAA animal model, it was found that the iliac lymph nodes around the abdominal aorta were significantly enlarged, and the number and lumen size of lymphatic vessels in the vessel wall were both significantly increased during the progression of AAA. Additionally, AAA was significantly promoted by ligating lymphatic vessels, which caused lymphatic drainage obstruction around the abdominal aorta. Our findings have the potential to enhance knowledge about the development and diagnosis of AAA.
本研究旨在通过生物信息学的方法探讨腹主动脉瘤(AAA)的淋巴管生成(LG)相关诊断指标,以及AAA进展过程中局部淋巴系统的改变及淋巴引流阻塞对AAA进展的影响。在基因表达集成芯片(Gene Expression Omnibus microarray)数据集中,鉴定出AAA患者组与健康供者组之间存在2957个差异表达基因。随后,将DEGs与LG基因进行交叉,得到93个基因。采用加权基因共表达网络分析(WGCNA)获得模块基因。模块基因与上述93个基因相交,得到26个基因。通过机器学习识别的5个中心基因(HSPA5、RAB10、RAB1A、RAF1、SMAD4)可通过nomogram和ROC评价作为AAA患者的候选诊断基因。进一步进行基因集富集分析(GSEA)和免疫浸润分析,分别了解这些候选基因的功能,探讨免疫在AAA中的作用。通过建立AAA动物模型发现,在AAA的进展过程中,腹主动脉周围的髂淋巴结明显增大,血管壁淋巴管数量和管腔大小均明显增加,结扎淋巴管可明显促进AAA,造成腹主动脉周围淋巴管引流阻塞。我们的发现有可能提高对AAA的发展和诊断的认识。
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Molecular and Cellular Probes
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