{"title":"Expression Patterns of Deubiquitinating Enzymes in Paclitaxel-Treated Lung Cancer Cells.","authors":"Hwa-Yeong Kim, Hae-Seul Choi, Kwang-Hyun Baek","doi":"10.1002/cbin.70072","DOIUrl":null,"url":null,"abstract":"<p><p>Lung cancer remains a leading cause of cancer-related mortality, underscoring the urgent need for more effective therapeutic strategies, particularly due to the frequent development of drug resistance. Paclitaxel, a widely used chemotherapeutic agent for non-small cell lung cancer (NSCLC), often faces resistance that limits its clinical efficacy. Therefore, identifying molecular markers that modulate paclitaxel responsiveness is critical. The ubiquitin-proteasome system (UPS), which regulates protein homeostasis, plays a role in cancer progression, apoptosis, and drug resistance, with deubiquitinating enzymes (DUBs), serving as key regulators. Recent studies suggest that targeting specific DUBs may enhance drug sensitivity. This study aimed to investigate the expression patterns of DUB genes in response to paclitaxel treatment. Multiplex RT-PCR and RT-qPCR analysis revealed that USP1, USP5, USP28, and USP34 were downregulated, whereas USP10 and USP36 were upregulated in paclitaxel-treated A549 cells. Western blot analysis confirmed changes in protein levels consistent with mRNA expression for all DUBs except USP10 and USP36, which displayed discordant patterns. Furthermore, paclitaxel-induced apoptosis was verified by altered levels of apoptotic and antiapoptotic proteins including PARP, caspase-3, Bax, Bcl-2, Bcl-XL, and p53. The identification of these DUB genes highlights their potential as biomarkers for predicting drug responsiveness and prognosis during paclitaxel treatment, thereby proposing a new direction for improving the therapeutic efficacy of paclitaxel in NSCLC.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology International","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/cbin.70072","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Lung cancer remains a leading cause of cancer-related mortality, underscoring the urgent need for more effective therapeutic strategies, particularly due to the frequent development of drug resistance. Paclitaxel, a widely used chemotherapeutic agent for non-small cell lung cancer (NSCLC), often faces resistance that limits its clinical efficacy. Therefore, identifying molecular markers that modulate paclitaxel responsiveness is critical. The ubiquitin-proteasome system (UPS), which regulates protein homeostasis, plays a role in cancer progression, apoptosis, and drug resistance, with deubiquitinating enzymes (DUBs), serving as key regulators. Recent studies suggest that targeting specific DUBs may enhance drug sensitivity. This study aimed to investigate the expression patterns of DUB genes in response to paclitaxel treatment. Multiplex RT-PCR and RT-qPCR analysis revealed that USP1, USP5, USP28, and USP34 were downregulated, whereas USP10 and USP36 were upregulated in paclitaxel-treated A549 cells. Western blot analysis confirmed changes in protein levels consistent with mRNA expression for all DUBs except USP10 and USP36, which displayed discordant patterns. Furthermore, paclitaxel-induced apoptosis was verified by altered levels of apoptotic and antiapoptotic proteins including PARP, caspase-3, Bax, Bcl-2, Bcl-XL, and p53. The identification of these DUB genes highlights their potential as biomarkers for predicting drug responsiveness and prognosis during paclitaxel treatment, thereby proposing a new direction for improving the therapeutic efficacy of paclitaxel in NSCLC.
期刊介绍:
Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect.
These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.