Mohammad Javad Bazyari , Ali Ahmadizad Firouzjaei , Seyed Mahdi Ahmadi , Mohsen Khorashadizadeh , Seyed Hamid Aghaee-Bakhtiari
{"title":"Exploiting network-based drug repositioning to target metastasis in colorectal cancer: In-Silico prediction and in-vitro evidence","authors":"Mohammad Javad Bazyari , Ali Ahmadizad Firouzjaei , Seyed Mahdi Ahmadi , Mohsen Khorashadizadeh , Seyed Hamid Aghaee-Bakhtiari","doi":"10.1016/j.mcp.2025.102053","DOIUrl":"10.1016/j.mcp.2025.102053","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"84 ","pages":"Article 102053"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226254","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}
Bashdar Mahmud Hussen , Snur Rasool Abdullah , Hazha Jamal Hidayat , Mark C. Glassy , Arash Safarzadeh , Alireza Komaki , Majid Samsami , Mohammad Taheri
{"title":"CRISPR/Cas as a tool to overcome drug resistance in cancer: From challenge to opportunity","authors":"Bashdar Mahmud Hussen , Snur Rasool Abdullah , Hazha Jamal Hidayat , Mark C. Glassy , Arash Safarzadeh , Alireza Komaki , Majid Samsami , Mohammad Taheri","doi":"10.1016/j.mcp.2025.102052","DOIUrl":"10.1016/j.mcp.2025.102052","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"84 ","pages":"Article 102052"},"PeriodicalIF":3.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187370","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}
Asma Vafadar , Negar Nayerain Jazi , Melika Eghtesadi , Sajad Ehtiati , Ahmad Movahedpour , Amir Savardashtaki
{"title":"Exosome biosensors for detection of ovarian cancer","authors":"Asma Vafadar , Negar Nayerain Jazi , Melika Eghtesadi , Sajad Ehtiati , Ahmad Movahedpour , Amir Savardashtaki","doi":"10.1016/j.mcp.2025.102051","DOIUrl":"10.1016/j.mcp.2025.102051","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"84 ","pages":"Article 102051"},"PeriodicalIF":3.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114922","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}
Zeyu Li , Chunfeng Zhang , Kuo Ma , Guangye Han , Weihang Song , Minghao Yue , Shuaiqi Chen
{"title":"Spatial and functional characterization of IL1RL1+ mast cells reveals immune regulatory roles in renal cancer","authors":"Zeyu Li , Chunfeng Zhang , Kuo Ma , Guangye Han , Weihang Song , Minghao Yue , Shuaiqi Chen","doi":"10.1016/j.mcp.2025.102049","DOIUrl":"10.1016/j.mcp.2025.102049","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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<sup>+</sup> mast cells may enhance CD8<sup>+</sup> cytotoxic T cell activation via the MHC-I signaling pathway. Spatial transcriptomics and multiplex immunohistochemistry (mIHC) confirmed the spatial co-localization of IL1RL1<sup>+</sup> 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.</div></div><div><h3>Conclusion</h3><div>Our findings highlight the immune-regulatory role of IL1RL1<sup>+</sup> mast cells in ccRCC. IL1RL1 may contribute to anti-tumor immunity through the modulation of antigen presentation and CD8<sup>+</sup> T cell activation, offering new insights into its potential as a prognostic biomarker and therapeutic target in renal cancer.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"84 ","pages":"Article 102049"},"PeriodicalIF":3.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006730","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}
Amir Hossein Aghayan , Ali Arab , Shadi Haddadi , Amir Atashi
{"title":"Non-coding RNAs in chronic lymphocytic leukemia: A systematic review and meta-analysis to decode the diagnostic potential","authors":"Amir Hossein Aghayan , Ali Arab , Shadi Haddadi , Amir Atashi","doi":"10.1016/j.mcp.2025.102048","DOIUrl":"10.1016/j.mcp.2025.102048","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"84 ","pages":"Article 102048"},"PeriodicalIF":3.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976163","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}
Yanyan Niu , Xu Zhang , Yuqing Chen , Xiaodong Chen , Xiaoyu Liu , Xiaodong Yao
{"title":"Secreted clusterin inhibits keloid formation by promoting fibroblast apoptosis","authors":"Yanyan Niu , Xu Zhang , Yuqing Chen , Xiaodong Chen , Xiaoyu Liu , Xiaodong Yao","doi":"10.1016/j.mcp.2025.102047","DOIUrl":"10.1016/j.mcp.2025.102047","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"83 ","pages":"Article 102047"},"PeriodicalIF":3.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904423","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}
{"title":"Establishment of CRISPR/Cas9 lineage tracking technology for pig embryos","authors":"Xiang-Qian Meng , Xue-Ling Xu , Yu Gao , Shou-Long Deng","doi":"10.1016/j.mcp.2025.102046","DOIUrl":"10.1016/j.mcp.2025.102046","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"83 ","pages":"Article 102046"},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840959","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}
{"title":"Differential expression of lncRNAs in lung cancer subgroups","authors":"Setareh Ataei , Bashdar Mahmud Hussen , Arda Kiani , Naghmeh Nazer , Arezou Sayad , Soudeh Ghafouri-Fard","doi":"10.1016/j.mcp.2025.102045","DOIUrl":"10.1016/j.mcp.2025.102045","url":null,"abstract":"<div><h3>Purpose</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the evaluated lncRNAs have potential as diagnostic biomarkers, but further research is needed to confirm their utility.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"83 ","pages":"Article 102045"},"PeriodicalIF":3.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812635","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}
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
{"title":"Copy number variations in urine cell-free DNA from bladder neoplasm patients","authors":"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","doi":"10.1016/j.mcp.2025.102044","DOIUrl":"10.1016/j.mcp.2025.102044","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"83 ","pages":"Article 102044"},"PeriodicalIF":2.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676347","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}