Cancer Cell International最新文献

{"title":"Unveiling the power of plumbagin: revitalizing exhausted T cells to combat tongue cancer.","authors":"Rongrong Zhang, Qingkun Jiang, Runying Guo, Ke Guo, Jiaxuan Qiu","doi":"10.1186/s12935-025-03892-x","DOIUrl":"10.1186/s12935-025-03892-x","url":null,"abstract":"<p><strong>Background: </strong>Tongue squamous cell carcinoma (TSCC), the most common form of oral cancer, has a poor prognosis associated with immune escape due to T cell exhaustion within the tumor microenvironment (TME). Numerous studies have demonstrated the anticancer properties of plumbagin; however, the correlation between plumbagin and TME-immune escape is unknown. This study aimed to evaluate the immunomodulatory effects of plumbagin in TSCC to facilitate the development of neoadjuvant immunotherapy strategies.</p><p><strong>Methods: </strong>We stimulated T cells with an antigen to induce a decrease in their cytotoxic function, an increase in programmed cell death-1(PD-1) expression, and exhaustion. Subsequently, plumbagin was utilized to target exhausted T cells, and its effect was evaluated using flow cytometry of apoptosis and PD-1 expression. Furthermore, a quantitative reverse transcription polymerase chain reaction measured the expression of immunoenhancing cytokines (Granzyme B, IFN-γ) and immunosuppressive cytokines (IL-10 and TGF-β). In vivo, plumbagin-treated homograft tongue cancer mouse and in situ tongue cancer model showed alterations in T cells, PD-1 expression and cytokines using flow cytometry and immunohistochemistry.</p><p><strong>Results: </strong>We found that plumbagin enhances the viability of exhausted T cells in vitro, enhancing apoptosis and decreasing PD-1 expression. In vivo, plumbagin inhibits TSCC growth, increases CD8⁺ T/CD4⁺ T cell ratio and decreases Treg cells and expression of PD-1. Furthermore, the expression of cytokines were regulated within the tumor.</p><p><strong>Conclusions: </strong>Plumbagin restores exhausted T cells'viability via multiple PD-L1/PD-1 axis, inhibiting TSCC immune escape and providing a theoretical foundation for immune microenvironment regulation.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"271"},"PeriodicalIF":5.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New models for MPNST: establishment and comprehensive characterization of two tumor cell lines.","authors":"Sara Ortega-Bertran, Edgar Creus-Bachiller, Miriam Magallón-Lorenz, Meritxell Carrió, Bernat Gel, Alberto Villanueva, Juan Carlos Lopez-Gutierrez, Anna Estival, Eduard Serra, Juana Fernández-Rodríguez, Conxi Lázaro","doi":"10.1186/s12935-025-03845-4","DOIUrl":"10.1186/s12935-025-03845-4","url":null,"abstract":"<p><strong>Background: </strong>Malignant peripheral nerve sheath tumors (MPNSTs) are rare, invasive, and aggressive soft tissue sarcomas arising from peripheral nerves. They may occur sporadically or in association with Neurofibromatosis type 1 (NF1), in which they are the leading cause of mortality. Currently, there are no effective therapies other than surgery. Therefore, tumor-derived cell lines are essential for testing new therapeutic strategies, especially when used in parallel with in vivo models. In this study, we present two new MPNST cell lines and two patient-derived orthotopic xenograft (PDOX) models from a sporadic (SP-10) and an NF1-related (NF1-18B) MPNST patient to increase the number of available preclinical models for in vitro and in vivo drug testing.</p><p><strong>Methods: </strong>The cell lines were isolated and extensively characterized genetically (tumor suppressor gene mutation status, DNA content), phenotypically (cell morphology, marker expression), and functionally (proliferation rate, colony formation capacity, migration rate, tumorigenic ability). We validated the models by comparing the genomic (copy number variation profile) and histological characteristics of the cell lines and PDOX tumors with their corresponding patient tumors.</p><p><strong>Results: </strong>The new cell lines and PDOXs tumors exhibited similar genomic copy number variation profiles, histological patterns, and marker expressions as the patient tumors, validating them as faithful models. Interestingly, the NF1-18B cell model presented two cell subpopulations with different ploidy states (one < 3n and the other 4n) and functional features in vitro. NF1-18B 4n, along with SP-10 cell lines, exhibited in vitro functional hallmarks of MPNSTs, including high proliferation and migration rates and colony forming ability. However, only the SP-10 model exhibited aggressive tumorigenicity in athymic mice. In contrast, the NF1-18B < 3n showed a low migration rate and did not form colonies or aggregates in vitro.</p><p><strong>Conclusions: </strong>The newly established MPNST cell lines, along with their corresponding PDOX models, serve as valuable tools for both in vitro and in vivo testing of novel therapeutic agents. Notably, the SP-10 cell line model represents one of the few documented cases isolated from a genuine \"classic\" MPNST.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"268"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-invasive colorectal cancer biomarkers: HAND2 and GPM6A methylation in circulating tumour DNA.","authors":"Amir Mahdi Nili, Kamal Mohammadian, Fatemeh Namazi Nanehkaran, Faranak Jamshidian, Arash Moradi, Shahla Mohammad Ganji","doi":"10.1186/s12935-025-03898-5","DOIUrl":"10.1186/s12935-025-03898-5","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"269"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental interpretation of the impact of vehicle emissions on prostate cancer progression.","authors":"Bingzheng An, Shuo Chen, Chen Zhang, Junyan Wang, Zhaoxin Guo, Ze Gao","doi":"10.1186/s12935-025-03906-8","DOIUrl":"10.1186/s12935-025-03906-8","url":null,"abstract":"<p><strong>Objective: </strong>Vehicle emissions (VEs) are considered important causes of air pollution in cities. This study aims to analyze the role of VEs in the progression of prostate cancer (PCa).</p><p><strong>Methods: </strong>We used the CTD database to obtain genes associated with VEs in prostate cancer to explore the associations between VEs and prostate cancer. LASSO regression analysis was subsequently used to construct a novel VEs-related progression model in the TCGA and GEO databases. Differences in the progression-free interval (PFI), clinical characteristics and immune characteristics were compared among patients with different VEs score. Finally, we confirmed that the changes of DNMT3B after VEs mediation and that DNMT3B promoted the progression of prostate cancer by preliminary experiments.</p><p><strong>Results: </strong>The analysis of VEs-enriched diseases revealed the most significant enrichment in the prostate cancer pathway. The GO enrichment analysis observed that VEs affected multiple signaling pathways and biological processes in PCa. On the basis of VEs-associated genes, we relied on the VEs scoring model to accurately evaluate the PFI (p < 0.05). In patients with high VEs scores, tumor mutation burden (TMB) (R = 0.29, p < 0.001) and the cytolytic activity (CYT) (R = 0.161, p < 0.001) scores were increased, as was the expression of immunosuppressive ligands. Functional experiments showed that knockdown of DNMT3B inhibited the proliferation, colony formation and migration of prostate cancer cells in vitro. In addition, we found that DNMT3B expression was significantly increased in tumor cells after VEs treatment.</p><p><strong>Conclusions: </strong>This study presents unique opinions into the impact of VEs on prostate cancer progression and highlights the need for more in-depth exploration of the mechanistic link between VEs and prostate cancer progression.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"270"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining cancer care: harnessing circulating tumor cells' potential for improved diagnosis and prognosis.","authors":"Divya Janjua, Apoorva Chaudhary, Udit Joshi, Tanya Tripathi, Vinita Kumar Jaggi, Alok Chandra Bharti","doi":"10.1186/s12935-025-03883-y","DOIUrl":"10.1186/s12935-025-03883-y","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs) represent a small but clinically relevant pool of cells from tumors that can be sampled with minimally-invasive liquid biopsy procedures. They are dynamic and poorly-defined transition state of cancer cells, offering vital insights into tumor progression and metastasis. CTC frequencies are emerging as real-time means for therapeutic monitoring and patient stratification across different malignancies. However, their detection, isolation, and characterization pose a major challenge leading to variation in their counts that limit their clinical utility. This review delves into the key parameter, CTC counts, which often correlate with clinical outcomes. Further, it highlights the significance of culturing CTCs in vitro and employing CTC-derived xenograft (CDX) models to obtain in vivo insights into tumor biology, treatment efficacy, and personalized medicine strategies. The review examines the role of CTCs as diagnostic, prognostic, and therapeutic monitoring marker for different cancers. It also discusses the opportunities in CTC-directed clinical utility and associated limitations such as CTC heterogeneity and technological variations among different isolation strategies that hinder their widespread implementation. Hence, it underscores the evolving importance of CTCs in clinical oncology.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"267"},"PeriodicalIF":5.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of S1PR1 in VEGF-exosomes mediated resistance of hepatocellular carcinoma to anti-angiogenesis therapy.","authors":"Xinghong Yao, Min Tang, Liang Li, Ye Zeng","doi":"10.1186/s12935-025-03907-7","DOIUrl":"10.1186/s12935-025-03907-7","url":null,"abstract":"<p><strong>Background: </strong>Anti-angiogenesis therapy (AAT) triggers vascular endothelial growth factor (VEGF)-exosomes secretion from tumor-associated endothelial cells (TAECs) for hepatocellular carcinoma (HCC) tubulogenesis and metastasis. Sphingosine-1-phosphate receptor 1 (S1PR1) has been implicated in HCC progression, but it was targeted by microRNA-9 (miR-9) that might mediate the formation of TAECs. This study aims to investigate the role of miR-9 and VEGF-exosomes in S1PR1-mediated HCC progression and resistance to AAT.</p><p><strong>Methods: </strong>The expression and distribution of miR-9 in HCC tissues were analyzed using qRT-PCR and fluorescence in situ hybridization (FISH). The impact of S1PR1 knockdown on VEGF-exosome uptake, as well as miR-9 and VEGF-exosome-induced epithelial-mesenchymal transition (EMT), migration, and invasion of HCC cells, was assessed by Transwell assays, fluorescence microscopy, and Western blotting.</p><p><strong>Results: </strong>miR-9 expression was significantly upregulated in HCC tissues and selectively localized in CD34⁺ endothelial cells within paracancerous microvessels, suggesting its role in TAEC transformation.miR-9 promoted EMT and enhanced HCC cell migration and invasion, effects that were further potentiated by VEGF-exosomes. S1PR1 knockdown significantly inhibited VEGF-exosome uptake and suppressed miR-9- and VEGF-exosome-induced EMT, migration, and invasion of HCC cells.</p><p><strong>Conclusion: </strong>In conclusion, miR-9 facilitates HCC progression by enhancing tumor malignancy and promoting AAT resistance through TAEC-mediated VEGF-exosome secretion. S1PR1 is a critical mediator of this process, and its inhibition represents a potential therapeutic strategy to overcome AAT resistance in HCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"264"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EIF4A3-induced circPRKAR1B promotes esophageal squamous cell carcinoma progression through binding PKM2 to regulate NF-κB induced CCL3 secretion.","authors":"Shiji Li, Junji Ma, Wenxiu Jia, Yangyang Duan, Jingran Wang, Xiuning Zhang, Yan Han","doi":"10.1186/s12935-025-03905-9","DOIUrl":"10.1186/s12935-025-03905-9","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) ranks as the sixth leading cause of cancer-related deaths globally, with over half of these cases occurring in China. However, the underlying molecular mechanisms of this disease are still not fully elucidated. Numerous circular RNAs (circRNAs) have been implicated in the initiation and progression of malignant tumors through diverse molecular pathways. Nevertheless, the clinical significance and functional roles of the majority of circRNAs associated with ESCC progression remain inadequately characterized. In the present study, we identified a novel circular RNA, designated as circPRKAR1B, which was found to be upregulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor prognosis in ESCC patients. Functionally, the overexpression of circPRKAR1B enhanced the proliferation and invasive capabilities of ESCC cells. Mechanistically, circPRKAR1B facilitates the progression of ESCC by interacting with PKM2, which in turn activates the NF-κB signaling pathway, thereby promoting the secretion of CCL3. Additionally, EIF4A3 promotes the expression of circPRKAR1B by binding to its downstream flanking sequences. These findings reveal a previously unrecognized role of circular RNA in the progression of ESCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"262"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and evaluation of metabolic mRNAs and key miRNAs in colorectal cancer liver metastasis.","authors":"Guanxuan Chen, Shiwen Wang, Meng Zhang, Wenna Shi, Ruoyu Wang, Wanqi Zhu","doi":"10.1186/s12935-025-03903-x","DOIUrl":"10.1186/s12935-025-03903-x","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) represents a major global health challenge due to its high lethality, largely attributable to liver metastasis. Despite the established correlation between metabolic reprogramming of cancer cells and their proliferation, invasion, and metastasis, the specific role of metabolism-associated mRNAs in the liver metastasis of CRC remains unelucidated.</p><p><strong>Methods: </strong>In our research, we procured and analyzed CRC liver metastasis-associated datasets from the GEO database. Subsequently, we employed Weighted Gene Co-expression Network Analysis (WGCNA) to construct an integrated co-expression network of mRNAs and miRNAs, facilitating the identification of pivotal mRNAs and miRNAs. We screened the featured genes using a machine-learning technique, followed by an evaluation of their diagnostic potential for CRC liver metastasis. Additionally, we conducted a functional enrichment analysis and constructed a network of miRNA-targeted mRNAs. Lastly, leveraging the UCSC Xena database, we assessed the correlation between core mRNAs and the clinical attributes and prognosis of CRC patients. Clinical samples from CRC patients and healthy volunteers were collected for validation using qRT-PCR.</p><p><strong>Results: </strong>Our study identified 12 mRNAs and 4 miRNAs significantly associated with CRC liver metastasis. Functional enrichment analysis indicated that these key genes were intricately linked with biological processes like lipid transport, homeostasis, and metabolism. By implementing LASSO and SVM algorithms, we pinpointed six core mRNAs from the key mRNAs. Their expression patterns and diagnostic performance were validated across multiple datasets. Particularly, CAV1 showed significant diagnostic performance to discern between CRC and CRC liver metastasis samples. Additionally, we discerned two key miRNAs (hsa-miR-1246 and hsa-miR-1290) exhibiting diagnostic performance. Lastly, our findings indicate a significant association between AGT, FABP4, and GPD1L and the prognosis of CRC patients with liver metastasis. PCR validation in 40 paired tissue samples showed downregulation of CAV1 and upregulation of miRNA-1290 in CRC tissues of patients with liver metastasis.</p><p><strong>Conclusions: </strong>This investigation identified modular genes and miRNAs linked to CRC liver metastasis, along with metabolism-associated differentially expressed mRNAs. These pivotal mRNAs and miRNAs could be instrumental in elucidating the biological mechanisms underpinning CRC liver metastasis and suggesting candidate biomarkers.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"265"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medicinal plants: nutritional, immunological and therapeutic role in treating cancer-related malnutrition: a comprehensive review.","authors":"Mohamed T El-Saadony, Samar Sami Alkafaas, Ahmed M Saad, Dina Mostafa Mohammed, Sameh A Korma, Heba M Salem, Taia A Abd El-Mageed, Mohamed I Elsalahaty, Sara Samy Elkafas, Walid F A Mosa, Ahmed Ezzat Ahmed, Essam H Ibrahim, Fawze Alnadari, Betty T Mathew, Alaa S Abdelhamid, Sahar F Allaban, Samah A Loutfy, Soumya Ghosh, Hanya Y Assal, Marawan K El-Tarabily, Synan F AbuQamar, Khaled A El-Tarabily","doi":"10.1186/s12935-025-03720-2","DOIUrl":"10.1186/s12935-025-03720-2","url":null,"abstract":"<p><p>Cancer is the second leading cause of death globally, following microbial infection, with an estimated 16 million deaths projected by 2040. However, natural resources can potentially treat up to 60% of cancer cases. Various cancers, including those affecting the breast, prostate, stomach, colon, lung, liver, kidney, bone, skin, and blood, have strong dietary connections regarding their occurrence and prevention. Cancer and its treatments, particularly chemotherapy, are closely associated with malnutrition in humans. The adverse effects of medical therapies and the disease itself often prevent patients with cancer from meeting their nutritional needs through regular food intake. The etiology of malnutrition in patients with cancer is complex and multifactorial, influenced by the type and location of cancer, disease stage, side effects of treatment, economic status, functional capacity, symptoms impacting nutrition, fasting requirements, inadequate dietary therapy, and awareness of the clinical staff regarding the role of dietary habits in diagnosis, treatment, and quality of life. Although there have been advances in drug-targeted therapies, they remain unelucidated, and therefore, this review aims to elucidate the relationship between cancer, chemical treatments, and malnutrition. In addition, it highlights the significant role of medicinal plants in treating various cancers and mitigating the adverse side effects of chemotherapy, offering a comprehensive understanding of their nutritional, immunological, and therapeutic benefits.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"266"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A LINC00472-encoded polypeptide impedes migration and proliferation through modulation of the HDAC2/SP1 axis in non-small cell lung cancer cells.","authors":"Lei Xu, Haoyong Kuang, Haodong Peng, Sen Wu, Yu Bai, Xiangbo Jia, Wenjian Yao","doi":"10.1186/s12935-025-03901-z","DOIUrl":"10.1186/s12935-025-03901-z","url":null,"abstract":"<p><strong>Objective: </strong>While long non-coding RNAs (lncRNAs) are increasingly recognized as sources of functional micropeptides, their roles in non-small cell lung cancer (NSCLC) remain poorly characterized. This study investigates the therapeutic potential and molecular mechanism of LINC00472-encoded polypeptide in NSCLC.</p><p><strong>Methods: </strong>Through integration of ribosome profiling, transcriptomics, and co-expression analysis, we systematically identified lncRNA-encoded polypeptides in NSCLC. Translational competence was validated via ribosome affinity purification (TRAP), Western blot, and immunofluorescence (IF). Functional assays (CCK-8, EdU, wound healing, transwell) and xenograft models assessed anti-tumor effects. HDAC2/SP1 interaction dynamics were analyzed by co-IP and luciferase reporter systems.</p><p><strong>Results: </strong>Multi-omics screening identified LINC00472 as a bifunctional transcript encoding a 15-aa polypeptide (LINC00472-ORF). LINC00472-ORF exhibited potent tumor-suppressive activity, reducing NSCLC proliferation and motility in vitro, while suppressing xenograft growth in vivo. Mechanistically, LINC00472-ORF disrupted HDAC2/SP1 interaction, inducing SP1 hyperacetylation, cytoplasmic retention, and transcriptional inactivation of downstream oncogenic genes.</p><p><strong>Conclusion: </strong>We unveil LINC00472-ORF as a dual-function therapeutic agent that targets the HDAC2/SP1 axis to inhibit NSCLC progression.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"263"},"PeriodicalIF":5.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}