Molecular and Cellular Probes最新文献_第2页

Exploiting network-based drug repositioning to target metastasis in colorectal cancer: In-Silico prediction and in-vitro evidence 利用基于网络的药物重新定位靶向结直肠癌转移：计算机预测和体外证据。

IF 3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-10-01 DOI: 10.1016/j.mcp.2025.102053

Mohammad Javad Bazyari , Ali Ahmadizad Firouzjaei , Seyed Mahdi Ahmadi , Mohsen Khorashadizadeh , Seyed Hamid Aghaee-Bakhtiari

Metastasis is a major challenge in colorectal cancer (CRC) treatment. The incidence of regional and distant stages has increased during the past decade and the 5-year survival of metastatic CRC patients is 20 %. Although there is a necessity to develop systematic treatment, the cost and time of novel drug discovery hinder this progress. Drug repositioning simplifies this process by accelerating regulatory processes in drug discovery. Here we used a systems biology approach to find key player genes in the metastasis. First, we found differentially expressed genes in metastatic tissue compared to primary tumors. Then, we constructed and analyzed the protein-protein interaction (PPI) network to find hub genes and subjected them to query in the DrugBank database. We found plasminogen (PLG) is the hub gene in the constructed PPI network and tranexamic acid (TXA) is its known inhibitor with clinically approved antifibrinolytic activity. Pathway enrichment analysis showed that PLG is involved in matrix remodeling, Platelet activation, and cell energy production through insulin-growth factor uptake in colorectal cancer cells which are important processes during metastasis. We further explored the CPTAC-COAD proteomics data and found that the PLG level is significantly higher in stage IV compared to stage I. Interestingly, we found that PLG is correlated with mutation rate. We then investigated the effect of TXA on SW480 cells' mobility and migration by scratch assay and transwell migration assay. Both assays indicated that TXA can significantly inhibit the cells’ migratory potential.

转移是结直肠癌（CRC）治疗的主要挑战。在过去十年中，局部和远处分期的发生率有所增加，转移性CRC患者的5年生存率为20%。虽然有必要开发系统的治疗方法，但新药发现的成本和时间阻碍了这一进展。药物重新定位通过加速药物发现的监管过程简化了这一过程。在这里，我们使用系统生物学方法来寻找转移的关键基因。首先，我们在转移组织中发现了与原发肿瘤相比的差异表达基因。然后，我们构建并分析了蛋白质-蛋白质相互作用（PPI）网络来寻找枢纽基因，并将其在DrugBank数据库中进行查询。我们发现纤溶酶原（PLG）是构建的PPI网络中的枢纽基因，氨甲环酸（TXA）是其已知的抑制剂，具有临床批准的抗纤溶活性。途径富集分析表明，PLG参与结肠直肠癌细胞基质重塑、血小板活化和通过胰岛素生长因子摄取产生细胞能量，这些都是转移过程中的重要过程。我们进一步研究了CPTAC-COAD蛋白质组学数据，发现PLG水平在IV期明显高于i期。有趣的是，我们发现PLG与突变率相关。然后，我们通过划痕实验和transwell迁移实验研究了TXA对SW480细胞迁移和迁移的影响。两项实验均表明，TXA能显著抑制细胞的迁移潜能。

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引用次数: 0

CRISPR/Cas as a tool to overcome drug resistance in cancer: From challenge to opportunity CRISPR/Cas作为战胜癌症耐药的工具：从挑战到机遇。

IF 3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-09-26 DOI: 10.1016/j.mcp.2025.102052

Bashdar Mahmud Hussen , Snur Rasool Abdullah , Hazha Jamal Hidayat , Mark C. Glassy , Arash Safarzadeh , Alireza Komaki , Majid Samsami , Mohammad Taheri

Drug resistance remains a significant challenge in cancer therapy, often resulting in treatment failure, tumor progression, and metastasis. The underlying resistance mechanisms—including genetic mutations, epigenetic alterations, and modifications in drug efflux pathways—are complex and not yet fully understood. This review explores the application of CRISPR-Cas gene editing technology in understanding and overcoming drug resistance in cancer. It focuses on how CRISPR can identify and target resistance-associated genes to restore drug sensitivity. CRISPR-based approaches enable precise genetic modifications that offer new insights into the molecular basis of drug resistance. The technology has shown promise in dissecting resistance mechanisms and developing targeted therapeutic strategies. Nevertheless, key limitations such as inefficient delivery systems, off-target effects, and limited specificity hinder clinical translation. Current efforts focus on improving guide RNA design, creating more effective delivery vectors, and integrating CRISPR with existing treatments. CRISPR-Cas technology holds significant potential to address drug resistance in cancer by enabling targeted genetic interventions. Continued advancements are required to enhance its safety, specificity, and delivery, paving the way for its integration into future clinical applications.

耐药仍然是癌症治疗中的一个重大挑战，经常导致治疗失败、肿瘤进展和转移。潜在的耐药机制——包括基因突变、表观遗传改变和药物外排途径的改变——是复杂的，尚未完全了解。本文综述了CRISPR-Cas基因编辑技术在了解和克服癌症耐药中的应用。它的重点是CRISPR如何识别和靶向耐药性相关基因以恢复药物敏感性。基于crispr的方法实现了精确的基因修饰，为耐药性的分子基础提供了新的见解。该技术在解剖耐药机制和开发靶向治疗策略方面显示出前景。然而，关键的限制，如低效率的输送系统，脱靶效应和有限的特异性阻碍了临床翻译。目前的工作重点是改进引导RNA设计，创造更有效的传递载体，以及将CRISPR与现有治疗方法结合起来。CRISPR-Cas技术通过实现靶向基因干预，具有解决癌症耐药问题的巨大潜力。需要持续的进步来增强其安全性、特异性和递送，为其整合到未来的临床应用铺平道路。

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引用次数: 0

Exosome biosensors for detection of ovarian cancer 检测卵巢癌的外泌体生物传感器。

IF 3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-09-19 DOI: 10.1016/j.mcp.2025.102051

Asma Vafadar , Negar Nayerain Jazi , Melika Eghtesadi , Sajad Ehtiati , Ahmad Movahedpour , Amir Savardashtaki

Ovarian cancer (OC) is one of the most aggressive gynecologic malignancies, largely due to its asymptomatic progression and frequent diagnosis at an advanced stage. Early detection is essential for improving patient survival rates. Exosomes, small extracellular vesicles secreted by cells, are actively involved in OC progression and have been recognized as potential biomarkers for early diagnosis. Over the past decade, advancements in exosome research have emphasized the need for detection methods that are not only sensitive and reliable but also practical for clinical use. However, conventional approaches often face challenges such as limited sensitivity and complex sample preparation. Biosensors have emerged as a promising alternative, offering benefits such as non-invasiveness and improved analytical performance. This review examines recent developments in electrochemical, optical, and electrical biosensors for detecting OC-related exosomes, discussing their sensitivity, specificity, and potential applications in clinical settings.

卵巢癌（OC）是最具侵袭性的妇科恶性肿瘤之一，主要是由于其无症状进展和经常在晚期诊断。早期发现对提高患者存活率至关重要。外泌体是细胞分泌的小细胞外囊泡，积极参与肿瘤的进展，被认为是早期诊断的潜在生物标志物。在过去的十年中，外泌体研究的进展强调了对检测方法的需求，这种检测方法不仅敏感可靠，而且对临床应用也很实用。然而，传统方法经常面临诸如灵敏度有限和样品制备复杂等挑战。生物传感器已经成为一种很有前途的替代方案，它提供了诸如非侵入性和改进的分析性能等好处。本文综述了用于检测oc相关外泌体的电化学、光学和电学生物传感器的最新进展，讨论了它们的敏感性、特异性和在临床环境中的潜在应用。

引用次数: 0

Spatial and functional characterization of IL1RL1+ mast cells reveals immune regulatory roles in renal cancer IL1RL1+肥大细胞的空间和功能特征揭示了肾癌的免疫调节作用

IF 3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-09-03 DOI: 10.1016/j.mcp.2025.102049

Zeyu Li , Chunfeng Zhang , Kuo Ma , Guangye Han , Weihang Song , Minghao Yue , Shuaiqi Chen

Background

Interleukin-1 receptor-like 1 (IL1RL1, also known as ST2) plays a critical role in immune regulation. Pan-cancer analysis has revealed that IL1RL1 is closely associated with cellular immune functions; however, its role in clear cell renal cell carcinoma (ccRCC) and the tumor microenvironment (TME) remains poorly defined.

Methods

We analyzed IL1RL1 expression patterns using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) were employed to investigate the cellular localization and biological functions of IL1RL1 in ccRCC. In addition, IL1RL1 knockout experiments were conducted to explore its potential role in antigen presentation.

Results

Compared to adjacent normal tissues, IL1RL1 expression was significantly downregulated in renal cancer tissues. Higher IL1RL1 expression correlated with improved patient prognosis, suggesting its potential as an independent prognostic biomarker. IL1RL1 was predominantly expressed in mast cells, with higher levels observed in adjacent normal tissues than in tumor tissues, implying a regulatory role in tumor immunity. Subset analysis revealed that IL1RL1-high mast cells were enriched in immune-inflammatory functions, including leukocyte activation, chemokine production, and antigen presentation. Cell–cell communication analysis further demonstrated that IL1RL1⁺ mast cells may enhance CD8⁺ cytotoxic T cell activation via the MHC-I signaling pathway. Spatial transcriptomics and multiplex immunohistochemistry (mIHC) confirmed the spatial co-localization of IL1RL1⁺ mast cells and T cells within the TME. Furthermore, IL1RL1 knockout led to a reduction in HLA-A expression, providing functional evidence for its involvement in antigen presentation.

Conclusion

Our findings highlight the immune-regulatory role of IL1RL1⁺ mast cells in ccRCC. IL1RL1 may contribute to anti-tumor immunity through the modulation of antigen presentation and CD8⁺ T cell activation, offering new insights into its potential as a prognostic biomarker and therapeutic target in renal cancer.

背景：白细胞介素-1受体样1 （Interleukin-1 receptor-like 1, IL1RL1，又称ST2）在免疫调节中起关键作用。泛癌分析显示，IL1RL1与细胞免疫功能密切相关；然而，其在透明细胞肾细胞癌（ccRCC）和肿瘤微环境（TME）中的作用仍不清楚。方法：利用癌症基因组图谱（TCGA）和基因表达图谱（GEO）数据库的数据分析IL1RL1的表达模式。利用单细胞RNA测序（scRNA-seq）和空间转录组学（ST）研究IL1RL1在ccRCC中的细胞定位和生物学功能。此外，我们还进行了IL1RL1敲除实验，以探索其在抗原呈递中的潜在作用。结果：与邻近正常组织相比，肾癌组织中IL1RL1表达明显下调。较高的IL1RL1表达与患者预后改善相关，提示其作为独立预后生物标志物的潜力。IL1RL1主要在肥大细胞中表达，其在邻近正常组织中的表达水平高于在肿瘤组织中的表达水平，表明其在肿瘤免疫中具有调节作用。亚群分析显示，il1rl1高的肥大细胞具有丰富的免疫炎症功能，包括白细胞活化、趋化因子产生和抗原呈递。细胞间通讯分析进一步表明，IL1RL1+肥大细胞可能通过MHC-I信号通路增强CD8+细胞毒性T细胞的活化。空间转录组学和多重免疫组织化学（mIHC）证实了IL1RL1+肥大细胞和T细胞在TME内的空间共定位。此外，IL1RL1敲除导致HLA-A表达减少，为其参与抗原递呈提供了功能证据。结论：我们的研究结果强调了IL1RL1+肥大细胞在ccRCC中的免疫调节作用。IL1RL1可能通过调节抗原呈递和CD8+ T细胞活化来促进抗肿瘤免疫，这为其作为肾癌预后生物标志物和治疗靶点的潜力提供了新的见解。

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引用次数: 0

Non-coding RNAs in chronic lymphocytic leukemia: A systematic review and meta-analysis to decode the diagnostic potential 慢性淋巴细胞白血病中的非编码rna：一项系统综述和解码诊断潜力的荟萃分析。

IF 3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-08-30 DOI: 10.1016/j.mcp.2025.102048

Amir Hossein Aghayan , Ali Arab , Shadi Haddadi , Amir Atashi

Background

Chronic lymphocytic leukemia (CLL) comprises around 25–30 % of leukemia cases in the West. Emerging evidence underscores the role of non-coding RNAs (ncRNAs) like miRNAs, lncRNAs, and CircRNAs in CLL pathogenesis and regulation. The unique properties of ncRNAs have given the potential as non-invasive diagnostic biomarkers for CLL.

Methods

PubMed, Web of Science, Scopus, ProQuest, and Embase databases were searched (from inception up to January 2024) for studies addressing the correlation of ncRNA expression levels with diagnosis of CLL. The QUADAS-2 tool was employed to evaluate the risk of bias in the included studies. The GRADE approach evaluated the certainty of the evidence for diagnostic test accuracy.

Results

A total of 14 studies including 934 CLL patients were analyzed. Evaluations focused on miRNAs and CircRNAs due to sufficient primary data. For miRNAs, pooled sensitivity: 0.84, specificity: 0.98, positive likelihood ratio (PLR): 42.19, negative likelihood ratio (NLR): 0.16, diagnostic odds ratio (DOR): 260.14; area under the curve (AUC): 0.96. For CircRNAs, pooled sensitivity: 0.69, specificity: 0.77, PLR: 3.01, NLR: 0.40, DOR: 7.51, AUC: 0.80. GRADE assessments indicated very low certainty of evidence for miRNAs and low certainty for CircRNAs.

Conclusion

Both miRNAs and CircRNAs appear to hold promise as non-invasive diagnostic biomarkers in CLL, with miRNAs demonstrating higher diagnostic performance. However, based on the GRADE assessments, the certainty of evidence may undermine the reliability of the pooled estimates. Future studies with rigorous design, larger sample sizes, and standardized protocols are essential to strengthen the certainty of evidence.

背景：慢性淋巴细胞白血病（CLL）约占西方白血病病例的25-30%。新出现的证据强调了非编码rna （ncRNAs）如miRNAs、lncRNAs和CircRNAs在CLL发病机制和调控中的作用。ncrna的独特特性赋予了其作为CLL非侵入性诊断生物标志物的潜力。方法：检索PubMed， Web of Science, Scopus， ProQuest和Embase数据库（从成立到2024年1月），寻找ncRNA表达水平与CLL诊断相关性的研究。采用QUADAS-2工具评估纳入研究的偏倚风险。GRADE方法评估诊断测试准确性证据的确定性。结果：共纳入14项研究，共纳入934例CLL患者。由于有足够的原始数据，评估主要集中在mirna和circrna上。对于miRNAs，合并敏感性：0.84，特异性：0.98，阳性似然比（PLR）： 42.19，阴性似然比（NLR）： 0.16，诊断优势比（DOR）： 260.14；曲线下面积（AUC）： 0.96。对于CircRNAs，总敏感性为0.69，特异性为0.77，PLR为3.01，NLR为0.40，DOR为7.51，AUC为0.80。GRADE评估表明，mirna和circrna的证据确定性非常低。结论：mirna和circrna似乎都有望成为CLL的非侵入性诊断生物标志物，其中mirna表现出更高的诊断性能。然而，基于GRADE评估，证据的确定性可能会破坏汇总估计的可靠性。严格设计、更大样本量和标准化方案的未来研究对于加强证据的确定性至关重要。

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引用次数: 0

Secreted clusterin inhibits keloid formation by promoting fibroblast apoptosis 分泌的聚簇素通过促进成纤维细胞凋亡抑制瘢痕疙瘩的形成

IF 3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-08-23 DOI: 10.1016/j.mcp.2025.102047

Yanyan Niu , Xu Zhang , Yuqing Chen , Xiaodong Chen , Xiaoyu Liu , Xiaodong Yao

Keloids are benign dermal proliferations resulting from excessive fibroblast activity that extends beyond the original site of injury. This study aims to investigate key biomarker genes associated with cell apoptosis and proliferation in the pathogenesis of keloids. Bioinformatic analysis of Gene Expression Omnibus datasets identified 122 differentially expressed genes (DEGs) in samples from keloid patients. Following the intersection with apoptosis-related genes (ARGs), three DEGs—ANLN, CLU, and SFRP2—were identified as keloid-associated ARGs. Among these, the expression of CLU was consistently reduced across both training and validation datasets. Experimental validation confirmed the expression alteration of CLU in keloid patient samples and further revealed that the expression of secreted CLU (sCLU) was significantly decreased in keloid fibroblasts. At the same time, BAX was down-regulated while BCL2 was up-regulated. Overexpression of sCLU in keloid derived primary fibroblasts significantly promoted apoptosis and reduced the viability of the cells, accompanied with up-regulated BAX and down-regulated BCL2, and fibrotic factor genes, such as collagen I, collagen III, α-SMA and CTGF. In contrast, serum levels of CLU did not differ significantly between keloid patients and non-related controls, suggesting limited utility of circulating CLU as a diagnostic biomarker. Taken together, these findings reveal a crucial role of sCLU in keloid pathogenesis, thereby presenting a potential tissue-level biomarker for keloid diagnosis and a promising therapeutic target.

瘢痕疙瘩是一种良性的皮肤增生，由过度的成纤维细胞活性引起，并延伸到原始损伤部位以外。本研究旨在探讨瘢痕疙瘩发病过程中与细胞凋亡和增殖相关的关键生物标志物基因。基因表达Omnibus数据集的生物信息学分析鉴定了瘢痕疙瘩患者样本中的122个差异表达基因（DEGs）。在与凋亡相关基因（ARGs）交叉后，三个degs——anln、CLU和sfrp2被鉴定为瘢痕疙瘩相关的ARGs。其中，CLU的表达在训练和验证数据集中都一致降低。实验验证证实了瘢痕疙瘩患者样本中CLU的表达改变，并进一步揭示了瘢痕疙瘩成纤维细胞中分泌CLU （sCLU）的表达显著降低。同时BAX下调，BCL2上调。瘢痕疙瘩源性原代成纤维细胞过表达sCLU可显著促进细胞凋亡，降低细胞活力，BAX上调，BCL2下调，I型胶原、III型胶原、α-SMA、CTGF等纤维化因子基因下调。相反，在瘢痕疙瘩患者和非相关对照组之间，血清CLU水平没有显著差异，表明循环CLU作为诊断生物标志物的效用有限。综上所述，这些发现揭示了sCLU在瘢痕疙瘩发病机制中的关键作用，从而提出了瘢痕疙瘩诊断的潜在组织水平生物标志物和有希望的治疗靶点。

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引用次数: 0

Establishment of CRISPR/Cas9 lineage tracking technology for pig embryos 猪胚胎CRISPR/Cas9谱系追踪技术的建立

IF 3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-08-13 DOI: 10.1016/j.mcp.2025.102046

Xiang-Qian Meng , Xue-Ling Xu , Yu Gao , Shou-Long Deng

Understanding tissue development in pigs is critical for biomedical research and genetic engineering, particularly for modeling human disease. However, tracing developmental origins and reconstructing lineage trees for pig cells remains a significant challenge. Here, we present a high-resolution lineage tracing system that combines molecular barcoding with single-cell transcriptomics in pigs. Our system combines two key components: DNA barcodes (three CRISPR/Cas9 target sites and an 8-base pair intBC) integrated into the genome via piggyBac transposition, and a constitutive Cas9-EGFP cassette stably integrated at the Rosa26 locus using CRISPR/Cas12a. By combining lineage barcodes with single-cell RNA sequencing (scRNA-seq), we constructed an evolutionary lineage recorder that captures distinct cell states across developmental or differentiation trajectories. This system provides an essential tool for the subsequent construction of complete porcine cell fate maps. Our work provides a tool for studying porcine developmental biology, but also helps to optimize regenerative medicine strategies and improve the design of genetically engineered animal models.

了解猪的组织发育对生物医学研究和基因工程，特别是对人类疾病建模至关重要。然而，追踪猪细胞的发育起源和重建谱系树仍然是一个重大挑战。在这里，我们提出了一个高分辨率谱系追踪系统，结合分子条形码和单细胞转录组学在猪。我们的系统结合了两个关键组件：DNA条形码（三个CRISPR/Cas9靶点和一个8碱基对intBC）通过piggyBac转位整合到基因组中，以及使用CRISPR/Cas12a稳定整合在Rosa26位点的组成型Cas9- egfp盒。通过将谱系条形码与单细胞RNA测序（scRNA-seq）相结合，我们构建了一个进化谱系记录器，可以捕获发育或分化轨迹中不同的细胞状态。该系统为后续构建完整的猪细胞命运图谱提供了重要的工具。我们的工作为研究猪的发育生物学提供了工具，也有助于优化再生医学策略和改进基因工程动物模型的设计。

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引用次数: 0

Differential expression of lncRNAs in lung cancer subgroups lncrna在肺癌亚组中的差异表达。

IF 3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-08-07 DOI: 10.1016/j.mcp.2025.102045

Setareh Ataei , Bashdar Mahmud Hussen , Arda Kiani , Naghmeh Nazer , Arezou Sayad , Soudeh Ghafouri-Fard

Purpose

Long non-coding RNAs (lncRNAs) have emerged as promising candidates in lung cancer research. This study aimed to assess the expression of eight autophagy-related lncRNAs in lung cancer tissues compared to matched non-tumor samples and to evaluate their potential as diagnostic biomarkers.

Methods

We examined the expression levels of LINC01963, RAB11B-AS1, AC104083.1, PLBD1-AS1, AC005076.1, LOC105376805 (BX284668.5), AL132989.1, and HERPUD2-AS1 (AC018647.2) in lung cancer samples, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and compared them to their matched controls. Subgroup analyses were performed based on sex.

Results

All eight lncRNAs were upregulated in NSCLC samples compared with controls, with AC104083.1 and HERPUD2-AS1 showing the highest ratios of mean expression (19.86 and 14.60, respectively). In male patients, all lncRNAs were significantly overexpressed in tumor samples (p < 0.05), with AC104083.1 exhibiting the highest upregulation (ratio = 26.93). In female patients, although upregulation was observed, none of the lncRNAs reached statistical significance. In SCLC samples, most lncRNAs demonstrated strong upregulation trends; however, p-values ranged from 0.05 to 0.09, indicating borderline significance. PLBD1-AS1 showed the highest upregulation (ratio = 46.28), while LOC105376805 had minimal differential expression (ratio = 2.16, p = 0.23). Expression levels of these lncRNAs may help discriminate lung cancer samples from controls and could differentiate NSCLC from SCLC samples.

Conclusion

These findings suggest that the evaluated lncRNAs have potential as diagnostic biomarkers, but further research is needed to confirm their utility.

目的：长链非编码rna （lncRNAs）已成为肺癌研究中有希望的候选者。本研究旨在评估肺癌组织中与匹配的非肿瘤样本相比，8种自噬相关lncrna的表达，并评估其作为诊断生物标志物的潜力。方法：我们检测了LINC01963、RAB11B-AS1、AC104083.1、PLBD1-AS1、AC005076.1、LOC105376805 （BX284668.5）、AL132989.1和HERPUD2-AS1 （AC018647.2）在非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）样本中的表达水平，并将其与匹配对照进行比较。根据性别进行亚组分析。结果：与对照组相比，所有8种lncrna在NSCLC样本中均上调，其中AC104083.1和HERPUD2-AS1的平均表达率最高（分别为19.86和14.60）。在男性患者中，所有lncRNAs在肿瘤样本中均显著过表达（p < 0.05），其中AC104083.1上调幅度最大（比值= 26.93）。在女性患者中，虽然观察到上调，但没有lncrna达到统计学意义。在SCLC样本中，大多数lncrna表现出强烈的上调趋势；但p值在0.05 ~ 0.09之间，具有临界显著性。PLBD1-AS1表达差异最大（比值为46.28），LOC105376805表达差异最小（比值为2.16,p = 0.23）。这些lncrna的表达水平可能有助于区分肺癌样本和对照组，并可以区分NSCLC和SCLC样本。结论：这些研究结果表明，所评估的lncrna具有作为诊断性生物标志物的潜力，但需要进一步的研究来证实其实用性。

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引用次数: 0

Copy number variations in urine cell-free DNA from bladder neoplasm patients 膀胱肿瘤患者尿无细胞DNA拷贝数的变化。

IF 2.3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-07-18 DOI: 10.1016/j.mcp.2025.102044

Cuello Garcia Haider , Qichao Wang , Guangyue Wang , Yinfeng Wang , Yutong Fu , Zhoufan Zhang , Changling Cao , Fengcheng Xue , Haitao Liu , Qian Wang , Jie Zhou , Tingya Jiang , Jingyi Cao , Yang Zhou

Bladder cancer is a common malignancy, and its diagnosis is based on invasive procedures such as cystoscopy. Genetic aberrations play an important role in the development of many diseases, including bladder cancer. As a result, identifying the genetic basis of a disease can provide useful information for early diagnosis and therapy. Cell-free DNA (cfDNA) offers a non-invasive approach to extract genetic information, which could be valuable for establishing the genetic cause of bladder cancer. In this study, we analyzed copy number variations (CNV) in urine cfDNA from 20 patients, with cystoscopy confirmed bladder cancer, sequenced by next-generation sequencing (NGS) and their CNV examined using the whole genome sequence. Statistical analysis of the carcinoma samples included Wilcoxon and Chi-square tests (p ≤ 0.005). Different patterns in CNV were identified in Chromosomes 1, 2, 3, 5, 6, 8, 9, 10, 11, 12, 17, 19, and 20 with the chromosome cytobands showing significant difference in variation patterns in patient parameters, such as smoking habit, number of tumors, grade of the tumors, and invasiveness. The genes that exhibited distinct CNV in each chromosomal cytoband have been associated with the development and progression of various cancers including bladder cancer indicating the clinical significance of CNVs as a useful tool for disease diagnosis. Therefore, this study demonstrates that by using NGS, CNV in urine cfDNA can provide valuable information on the state of blader cancer which can be further utilized to investigate therapies or early diagnosis.

膀胱癌是一种常见的恶性肿瘤，其诊断是基于侵入性手术，如膀胱镜检查。遗传畸变在包括膀胱癌在内的许多疾病的发展中起着重要作用。因此，确定疾病的遗传基础可以为早期诊断和治疗提供有用的信息。无细胞DNA （cfDNA）提供了一种非侵入性的方法来提取遗传信息，这对于确定膀胱癌的遗传原因可能有价值。在这项研究中，我们分析了20例膀胱镜检查确诊的膀胱癌患者尿液cfDNA的拷贝数变异（CNV），采用下一代测序（NGS）测序，并使用全基因组序列检测其CNV。肿瘤样本的统计学分析采用Wilcoxon检验和卡方检验（p≤0.005）。在第1、2、3、5、6、8、9、10、11、12、17、19和20号染色体上发现了不同的CNV模式，染色体细胞带在患者吸烟习惯、肿瘤数量、肿瘤分级和侵袭性等参数上的变异模式存在显著差异。在每个染色体细胞带中表现出不同CNV的基因与包括膀胱癌在内的各种癌症的发生和进展相关，这表明CNV作为疾病诊断的有用工具具有临床意义。因此，本研究表明，通过NGS，尿cfDNA中的CNV可以提供有关膀胱癌状态的有价值的信息，可进一步用于研究治疗或早期诊断。

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引用次数: 0

Ubiquitin-specific peptidase 53 suppresses the tumorigenesis of breast cancer cells and its related gene analysis 泛素特异性肽酶53抑制乳腺癌细胞发生及其相关基因分析。

IF 2.3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-07-17 DOI: 10.1016/j.mcp.2025.102043

Hongbo Lan , Lina Peng , Fei Chen , Kun Xie , Futing Mu , Jingshuang Wang , Juanjuan Mei , Wenhui Yan

Background

Breast cancer (BC) remains the most common malignancy affecting women's health globally. Thus, elucidating the molecular mechanisms driving BC progression and identifying novel therapeutic targets is imperative. Ubiquitin-specific peptidase 53 (USP53) is a deubiquitinating enzyme reported to exert tumor-suppressive effects in several types of cancers. However, USP53 has been poorly studied in BC.

Methods

Based on the TCGA database and GTEx transcriptome data, differentially expressed genes in BC were screened, and the relationship between USP53 expression and BC characteristics and prognosis were analyzed. qRT-PCR, Western blot, and immunohistochemistry determined USP53 expression. After transfection, BC cells’ proliferation, migration, and invasion were assessed using CCK-8 and Transwell assay. A subcutaneous xenograft tumor model in nude mice was used to evaluate the in vivo effect of USP53. Besides, USP53 expression-associated immune cells were screened using the Cibersort package.

Results

USP53 expression was reduced in BC patients and showed potential diagnostic significance. Functionally, overexpressing USP53 inhibited BC cell proliferation, migration, and invasion, while silencing it promoted these malignant behaviors. In vivo, tumors derived from USP53-overexpressing cells grew more slowly and exhibited lower Ki67 expression. Additionally, we found that Tcm, T helper cells, Mast cells, and Eosinophils were positively associated with USP53 expression, whereas NK CD56dim cells and TReg were negatively associated with USP53 expression.

Conclusions

Together, we proved that USP53 was down-regulated in BC and weakened the malignant progression of BC cells both in vitro and in vivo. USP53 was also associated with a variety of immune cells. Our study suggested that USP53 may be a novel target for BC therapy.

背景：乳腺癌（BC）仍然是影响全球妇女健康的最常见恶性肿瘤。因此，阐明驱动BC进展的分子机制和确定新的治疗靶点是必要的。泛素特异性肽酶53 （USP53）是一种去泛素化酶，据报道在几种类型的癌症中发挥肿瘤抑制作用。然而，USP53在BC中的研究很少。方法：基于TCGA数据库和GTEx转录组数据，筛选BC中差异表达基因，分析USP53表达与BC特征及预后的关系。qRT-PCR、western blot和免疫组化检测USP53的表达。转染后，采用CCK-8和Transwell实验评估BC细胞的增殖、迁移和侵袭。采用裸鼠皮下移植瘤模型评价USP53在体内的作用。此外，使用Cibersort软件包筛选USP53表达相关的免疫细胞。结果：USP53在BC患者中表达降低，具有潜在的诊断意义。功能上，过表达USP53抑制了BC细胞的增殖、迁移和侵袭，而沉默USP53则促进了这些恶性行为。在体内，usp53过表达细胞衍生的肿瘤生长更慢，Ki67表达更低。此外，我们发现Tcm、T辅助细胞、肥大细胞和嗜酸性粒细胞与USP53表达呈正相关，而NK CD56dim细胞和TReg与USP53表达负相关。结论：我们共同证明了USP53在BC中下调，并在体外和体内减弱了BC细胞的恶性进展。USP53还与多种免疫细胞有关。我们的研究提示USP53可能是BC治疗的新靶点。

{"title":"Ubiquitin-specific peptidase 53 suppresses the tumorigenesis of breast cancer cells and its related gene analysis","authors":"Hongbo Lan , Lina Peng , Fei Chen , Kun Xie , Futing Mu , Jingshuang Wang , Juanjuan Mei , Wenhui Yan","doi":"10.1016/j.mcp.2025.102043","DOIUrl":"10.1016/j.mcp.2025.102043","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) remains the most common malignancy affecting women's health globally. Thus, elucidating the molecular mechanisms driving BC progression and identifying novel therapeutic targets is imperative. Ubiquitin-specific peptidase 53 (USP53) is a deubiquitinating enzyme reported to exert tumor-suppressive effects in several types of cancers. However, USP53 has been poorly studied in BC.</div></div><div><h3>Methods</h3><div>Based on the TCGA database and GTEx transcriptome data, differentially expressed genes in BC were screened, and the relationship between USP53 expression and BC characteristics and prognosis were analyzed. qRT-PCR, Western blot, and immunohistochemistry determined USP53 expression. After transfection, BC cells’ proliferation, migration, and invasion were assessed using CCK-8 and Transwell assay. A subcutaneous xenograft tumor model in nude mice was used to evaluate the <em>in vivo</em> effect of USP53. Besides, USP53 expression-associated immune cells were screened using the Cibersort package.</div></div><div><h3>Results</h3><div>USP53 expression was reduced in BC patients and showed potential diagnostic significance. Functionally, overexpressing USP53 inhibited BC cell proliferation, migration, and invasion, while silencing it promoted these malignant behaviors. <em>In vivo</em>, tumors derived from USP53-overexpressing cells grew more slowly and exhibited lower Ki67 expression. Additionally, we found that Tcm, T helper cells, Mast cells, and Eosinophils were positively associated with USP53 expression, whereas NK CD56dim cells and TReg were negatively associated with USP53 expression.</div></div><div><h3>Conclusions</h3><div>Together, we proved that USP53 was down-regulated in BC and weakened the malignant progression of BC cells both <em>in vitro</em> and <em>in vivo</em>. USP53 was also associated with a variety of immune cells. Our study suggested that USP53 may be a novel target for BC therapy.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"83 ","pages":"Article 102043"},"PeriodicalIF":2.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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