Current cancer drug targets最新文献

{"title":"Controversial Role of Opioids: From Pain Control to Cancer Recurrence in Breast Cancer.","authors":"Mudasir Maqbool, Gyas Khan, Liming Zhang, Md Sadique Hussain","doi":"10.2174/0115680096391788250610080609","DOIUrl":"10.2174/0115680096391788250610080609","url":null,"abstract":"<p><p>Opioids are widely used for pain management in breast cancer patients; however, their influence on tumor progression and recurrence remains controversial. Opioid receptors-mu (MOR), delta (DOR), and kappa (KOR)-play diverse roles in cancer biology, modulating tumor growth, im-mune responses, and angiogenesis. MOR activation is associated with increased proliferation, Epi-thelial-Mesenchymal Transition (EMT), and immunosuppression, contributing to an aggressive tu-mor phenotype. Conversely, KOR exhibits tumor-suppressive properties, reducing angiogenesis via VEGF inhibition. Emerging preclinical evidence suggests that opioids, particularly morphine, may facilitate breast cancer progression by enhancing cancer cell migration, angiogenesis, and immune evasion. Genetic variations in opioid receptor pathways, such as the OPRM1 A118G polymorphism, further complicate the opioid-cancer relationship, demonstrating population-dependent effects on pa-tient outcomes. In contrast, tramadol has shown potential immune-protective effects by preserving Natural Killer (NK) cell function and inhibiting adrenergic signaling; fentanyl and sufentanil exhibit variable impacts on tumor biology, necessitating further investigation. Clinical studies, however, re-main inconclusive regarding opioids #039; direct contribution to breast cancer recurrence, highlighting the need for targeted research. Opioid-sparing analgesic strategies, including multimodal pain manage-ment, regional anesthesia, and immunomodulatory agents, offer promising alternatives to mitigate potential oncogenic risks while ensuring adequate pain relief. Future studies integrating single-cell transcriptomics and tumor microenvironment analyses will be critical in elucidating the molecular impact of opioids in breast cancer. Personalized pain management approaches tailored to genetic and clinical profiles may optimize oncological outcomes while preserving analgesic efficacy.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Non-Coding RNAs in Regulating PD-L1 Expression in Breast Cancer: Emerging Insights and Implications.","authors":"Jianqin Zhu, Weijin Zhu, Xulin Zhou, Jingwen Hua, Xiaochun Sun","doi":"10.2174/0115680096376016250607151653","DOIUrl":"10.2174/0115680096376016250607151653","url":null,"abstract":"<p><p>The initiation and progression of breast cancer generally involve complex immune regulatory mechanisms, with increased expression of programmed cell death ligand 1 (PD-L1) as an essential factor for immune evasion and the formation of a tumor-promoting immune microenvironment. Emerging evidence underscores the regulatory role of non-coding RNAs (ncRNAs) in modulating PD-L1 expression, influencing immune evasion, tumorigenesis, and therapy resistance in breast cancer. Therefore, it is crucial further to clarify alternative regula-tory mechanisms that control PD-L1 expression. The variations in PD-L1 expression among different breast cancer subtypes and the mechanisms by which ncRNAs regulate the expres-sion of PD-L1 are delineated. This study explores the potential and challenges of combining ncRNA-based therapy with PD-L1 inhibitors, offering insights into PD-L1 regulation and per-sonalized treatment strategies in breast cancer.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EVI5 Drives Lung Adenocarcinoma Progression through Modulation of the ERK1/2-c-Myc Signaling Axis.","authors":"Peipei Zhang, Xinyang Zhang, Tingting Cai, Yangyang Xu, Yiqing Xie, Chong Li","doi":"10.2174/0115680096384104250529115246","DOIUrl":"https://doi.org/10.2174/0115680096384104250529115246","url":null,"abstract":"<p><strong>Introduction: </strong>Lung adenocarcinoma (LUAD) remains a lethal disease worldwide with a poor prognosis. The ecotropic viral integration site 5 (EVI5) is a crucial oncogene and mediator of cell division processes, and it extensively participates in tumorigenesis and progression. However, the role of EVI5 in LUAD progression remains elusive. This study aimed to further explore the underlying mechanisms of EVI5's involvement in LUAD development.</p><p><strong>Methods: </strong>The GEO database was employed to investigate the expression of EVI5 in LUAD and normal tissues, while the Kaplan-Meier Plotter database was utilized to assess its correlation with patient prognosis. Stable cell lines with EVI5 knockout and overexpression were constructed, and a Western blot was performed to detect EVI5 protein expression levels to validate the successful establishment of the stable cell lines. The abilities of proliferation, invasion, and migration of LUAD cells after transfection were analyzed using CCK-8, colony formation, transwell, and wound healing assays. Western blotting, immunofluorescence, and qRT-PCR were further carried out to measure the protein and mRNA expression levels associated with the ERK1/2-c-Myc signaling pathway. Finally, functional rescue experiments were performed on LUAD cells to further explore and verify the signaling pathway.</p><p><strong>Results: </strong>EVI5 was found to be highly expressed in lung adenocarcinoma tissues and correlated with poor prognosis. EVI5 overexpression promoted the malignant behavior of lung adeno-carcinoma, whereas its knockout produced the opposite effect. Mechanistically, ERK1/2-c-Myc, the key signaling pathway in the malignant progression of LUAD, was further validated by an ERK1/2 pathway inhibitor.</p><p><strong>Conclusion: </strong>Our study demonstrated for the first time that EVI5 promotes malignant progression through the activation of the ERK1/2-c-Myc signaling axis, providing new insights into the pathogenesis of LUAD.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Bispecific Antibodies and Clinical Research Advances in Lung Cancer.","authors":"Jie Yang, Yangyueying Liang, Meiying Zhu, Yuan Meng, Xuerui Wang, Minghui Yu, Longhui Li, Fanming Kong","doi":"10.2174/0115680096353819250127065001","DOIUrl":"https://doi.org/10.2174/0115680096353819250127065001","url":null,"abstract":"<p><p>Lung cancer is an aggressive malignancy and one of the leading causes of cancer-related mortality worldwide. Compared with traditional treatments, the development of pre-cision treatment programs, such as targeted therapy and immunotherapy, has progressively transformed non-small cell lung cancer (NSCLC) with driver mutations, becoming a clini-cally controllable chronic disease. Among the treatments for lung cancer, monospecific anti-bodies gradually show effectiveness but also expose their susceptibility to drug resistance, off-target effects, and other limitations. Therefore, bispecific antibodies have been developed, which have two different antigen-binding sites so that they can bind two distinct antigens or two distinct epitopes of the same antigen with adjustable specificity and do not easily produce drug resistance. This article reviews the design strategies and mechanism of bispecific anti-bodies, summarizes the latest progress in clinical trials involving bispecific antibodies for lung cancer, and analyzes the current challenges and future directions in this area of research.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Pan-cancer Analysis and Experimental Verification of EGLN Family: Potential Biomarkers in Cervical Cancer.","authors":"Dongli Zhang, Ruifang Fu, Guixia Sun, Junfang Yan, Xiaofeng Yang","doi":"10.2174/0115680096362252250527060004","DOIUrl":"https://doi.org/10.2174/0115680096362252250527060004","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia plays a crucial role in malignant tumor formation, primarily mediated by hypoxia-inducible factors (HIFs). Despite extensive research, the complexities and prognostic implications of the EGLN gene family (EGLN1, EGLN2, EGLN3) in cancers remain unclear.</p><p><strong>Methods: </strong>Utilizing public databases (TCGA, GTEx, TARGET, GEO) and bioinformatics tools, a comprehensive analysis of EGLN genes across various cancer types was conducted. Gene ex-pression, mutation data, stemness scores, and clinical information were integrated to evaluate the mutation landscape, expression levels, and prognostic values of EGLNs. Enrichment and pathway analyses explored EGLN-associated biological processes and functional networks. ssGSEA con-structed EGLN scores for prognostic evaluation. Colocalization analysis combined eQTL and GWAS data to investigate genetic variations in cervical cancer. Immunohistochemistry validated EGLN expression in cervical cancer tissues.</p><p><strong>Results: </strong>EGLN genes showed differential expression across cancer types. EGLN1 overexpres-sion was associated with worse survival in cervical squamous cell carcinoma (CESC), pancreatic adenocarcinoma (PAAD), and neuroblastoma (NB), while EGLN3 was linked to poor survival in CESC, lung adenocarcinoma (LUAD), and kidney cancers. EGLNs also demonstrated varied roles in modulating tumor immune activity and heterogeneity.</p><p><strong>Conclusion: </strong>This study provides new insights into EGLN biology and identifies EGLN1 as a potential biomarker for cervical cancer.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raddeanoside R13 Inhibits Proliferation, Invasion, and Metastasis of Gastric Cancer Cells Based on Network Pharmacology and Experimental Validation.","authors":"Tiantian Zhao, Qiong Wu, Mingxu Da, Chenglou Zhu","doi":"10.2174/0115680096379893250523102125","DOIUrl":"https://doi.org/10.2174/0115680096379893250523102125","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore the potential mechanisms by which Rad-deanoside R13 (R13) inhibits the proliferation, invasion, and metastasis of gastric cancer (GC) cells through network pharmacology analysis and experimental validation.</p><p><strong>Methods: </strong>First, network pharmacology was used to explore the potential mechanisms of R13 in treating gastric cancer. The effects of R13 on GC cell proliferation were assessed using CCK-8 and colony formation assays. Apoptosis was measured by flow cytometry, while the effects of R13 on invasion and metastasis were evaluated through wound healing and Transwell invasion assays. Finally, Western blotting was performed to investigate the impact of R13 on the expression of epithelial-to-mesenchymal transition (EMT) markers, PI3K/AKT signaling pathway proteins, and apoptosis-related proteins in GC cells.</p><p><strong>Results: </strong>A total of 58 potential targets of R13 in the treatment of GC were identified. R13 was found to affect the development of GC by regulating pathways, such as NFKB1, mTOR, apoptosis, and the PI3K-Akt signaling pathway. In vitro experiments confirmed that R13 inhibited the proliferation, invasion, and metastasis of GC cells while promoting apoptosis. Additionally, we found that R13 suppressed the EMT of GC cells and reduced the phos-phorylation levels of PI3K, Akt, and mTOR. When this pathway was activated, it partially reversed these effects.</p><p><strong>Conclusion: </strong>R13 inhibited the proliferation, invasion, and metastasis of GC cells while in-ducing apoptosis. Furthermore, R13 may suppress the EMT process in GC cells by inhibit-ing the PI3K/Akt/mTOR signaling pathway. These findings provide a foundation for the potential use of R13 as a therapeutic strategy for gastric cancer.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles-Associated tRFs as Emerging Biomarkers in Breast Cancer.","authors":"Md Sadique Hussain, Liming Zhang, Sumel Ashique","doi":"10.2174/0115680096388071250527074008","DOIUrl":"https://doi.org/10.2174/0115680096388071250527074008","url":null,"abstract":"<p><p>Breast cancer (BC) remains a leading cause of cancer-related mortality among women worldwide, underscoring the urgent need for sensitive, non-invasive biomarkers to improve diagnosis, prognosis, and treatment monitoring. Traditional biomarkers like ER, PR, and HER2 offer limited efficacy, particularly for heterogeneous subtypes such as triple-nega-tive breast cancer (TNBC). Extracellular vesicles (EVs), including exosomes and microvesi-cles, have emerged as promising biomarker carriers due to their stability and ability to encap-sulate diverse bioactive molecules reflective of the parental cell's state. Among EV cargoes, tRNA-derived fragments (tRFs), which are small non-coding RNAs produced by precise cleavage of tRNAs, have gained increasing attention. Once considered mere degradation prod-ucts, tRFs are now recognized for their roles in gene regulation, translation control, apoptosis modulation, and immune response. Recent studies have revealed the selective enrichment of tRFs within EVs, highlighting their role in intercellular communication in breast cancer. Dif-ferential expression of EV-associated tRFs correlates with BC subtype, stage, and patient prog-nosis, highlighting their potential as minimally invasive biomarkers. Specifically, altered lev-els of certain 5'- and 3'-tRFs in patient sera and tumor tissues have been associated with poor survival, metastasis, and therapeutic resistance. Despite these promising findings, gaps remain regarding the mechanisms of tRF sorting into EVs and their functional impact on the tumor microenvironment. This review systematically examines the current understanding of EV-as-sociated tRFs in breast cancer, emphasizing their clinical relevance, detection strategies, and translational potential. By addressing existing challenges, we aim to provide insights into the utility of EV-tRFs as novel biomarkers and therapeutic targets in BC.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etiology-based Molecular Characterization of Hepatocellular Carcinoma Reveals SQLE's Contribution to Immunosuppressive Microenvironment.","authors":"Kangkang Yu, Qisheng Zhong, Jubo Zhang, Chong Huang","doi":"10.2174/0115680096370558250514063841","DOIUrl":"https://doi.org/10.2174/0115680096370558250514063841","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a kind of fatal cancer with a variety of risk factors. However, a pan-etiology molecular characterization of HCC has not been explored.</p><p><strong>Objective: </strong>The objective of this study is to explore etiology-specific features of HCC and im-prove our understanding of tumorigenesis, thereby revealing potential therapeutic targets.</p><p><strong>Methods: </strong>RNA-seq, genetic alteration, copy number alteration, and clinicopathological data of The Cancer Genome Atlas -Liver Hepatocellular Carcinoma cohort were downloaded and explored. Immune-related features and single-cell and spatial transcriptomic data were adopted and analyzed.</p><p><strong>Results: </strong>Etiology-based analyses revealed that HCC with different etiologies showed different clinical features, including gender composition, ethnic composition, clinical stage distribution, and survival. In addition, distinct genetic alterations, copy number alterations, and tumor microenvironment were observed in HCC patients with different etiologies. Significantly enhanced expression of squalene epoxidase (SQLE) was observed in viral hepatitis-related HCC and was associated with poor tumor grade and overall survival. Correlation analysis revealed a negative relationship between SQLE expression and anti-tumor immunity. Single-cell and spatial transcriptomics demonstrated that SQLE contributed to reduced T cell and NK cell infiltration while increasing macrophage and monocyte infiltration.</p><p><strong>Conclusion: </strong>The current study demonstrated that HCC has etiology-specific clinical features, genetic alteration, copy number alteration, and tumor microenvironment. Overexpression of SQLE in viral hepatitis-related HCC correlate with poor clinical outcome and may contribute to reduce T cell and NK cell infiltration while increased macrophage and monocyte infiltration, which lead to immunosuppressive microenvironment and can be an actionable target.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Distinctiveness in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Cancer: Identifying Key Genomic Signatures through Differentially Expressed Gene Analysis.","authors":"Patrick Shi, Wenqiang Chen","doi":"10.2174/0115680096372957250322174718","DOIUrl":"https://doi.org/10.2174/0115680096372957250322174718","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the most commonly diagnosed cancer type and the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancer cases and includes two main subtypes: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Understanding the differences in genes causing the proliferation of LUAD and LUSC is key to advancing the diagnosis and targeted treatment development.</p><p><strong>Aims: </strong>The aim of this study was to identify candidate genes and potential tumorigenesis mechanisms distinguishing LUAD and LUSC.</p><p><strong>Methods: </strong>Three pooled transcriptomic datasets (GSE10245, GSE37745, and GSE43580) were analyzed from the Gene Expression Omnibus (GEO) database, with each dataset statistically tested for differentially expressed genes (DEGs). DEGs between lung LUAD and LUSC of the three datasets were analyzed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network was constructed to screen candidate genes.</p><p><strong>Results: </strong>This study identified 138 shared DEGs among three patient-level gene expression datasets, containing 39 upregulated genes and 99 downregulated genes. The GO and KEGG enrichment analysis results showed the functions of DEGs to be mainly associated with epidermis development, cornified envelope, structural constituent of epidermis, and estrogen signaling pathway. Finally, through the PPI network, eight core genes were identified, including KRT14, KRT5, KRT6A, KRT16, SPRR1A, SPRR1B, SPRR3, and KRT6B.</p><p><strong>Conclusion: </strong>We have elucidated key genes and molecular mechanisms linked to NSCLC subtypes. These findings have the potential to facilitate improved diagnostic and therapeutic targets for LUAD and LUSC biomarkers.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trimethylamine N-oxide Impairs Oocyte Maturation and Embryogenesis via NF-κB/NLRP3 Pathway Modulation.","authors":"Fengping He, Yongmei Zhang, Yanle Guo, Tizhen Yan, Jiwu Lou","doi":"10.2174/0115680096364675250419135908","DOIUrl":"https://doi.org/10.2174/0115680096364675250419135908","url":null,"abstract":"<p><strong>Background: </strong>The role of Trimethylamine N-oxide (TMAO) in oocyte maturation and embryogenesis remains unclear, particularly its impact on ovarian granulosa cells (OGCs) and its underlying mechanisms.</p><p><strong>Methods: </strong>This study examined the effects of TMAO (100-400 μmol/L) on oocyte maturation, cumulus cell expansion, mitochondrial distribution, and embryonic development in vitro and in a BALB/c mouse model. The involvement of the NF-κB/NLRP3 signaling pathway in TMAO-induced ovarian dysfunction was assessed using Western blotting and gene expression analyses. The potential therapeutic effect of miRNA-146, an NF-κB inhibitor, was also explored.</p><p><strong>Results: </strong>Western blotting confirmed that TMAO activates the NF-κB signaling pathway and induces the synthesis of caspase 3 and NLRP3 complexes. However, pretreatment with miRNA-146, an NF-κB inhibitor, significantly reduced inflammation and inflammatory gene expression during TMAO therapy. Additionally, miRNA-146 pretreatment promoted oocyte maturation by suppressing NF-κB/NLRP3 activation, OGCs apoptotic inflammatory factor expression, and the gene expression of NF-κB, caspase 3, and NLRP3.</p><p><strong>Conclusion: </strong>Findings demonstrate that TMAO disrupts oocyte development through NF- κB/NLRP3 activation, contributing to ovarian dysfunction. Notably, targeting TMAO and its downstream signaling could serve as a novel therapeutic strategy for premature ovarian insufficiency (POI).</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}