Kang Li, Yuxuan Yi, Rongsong Ling, Caihua Zhang, Zhihui Zhang, Yue Wang, Ganping Wang, Jie Chen, Maosheng Cheng, Shuang Chen
{"title":"PCIF1通过m6am介导的MTF2翻译抑制驱动食管鳞状细胞癌的进展","authors":"Kang Li, Yuxuan Yi, Rongsong Ling, Caihua Zhang, Zhihui Zhang, Yue Wang, Ganping Wang, Jie Chen, Maosheng Cheng, Shuang Chen","doi":"10.1002/ctm2.70286","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <p>Oesophageal squamous cell carcinoma (OSCC) represents a highly aggressive malignancy with limited therapeutic options and poor prognosis. This study uncovers PCIF1 as a critical driver of OSCC progression via m6Am RNA modification, leading to translational repression of the tumour suppressor MTF2. Our results demonstrate that PCIF1 selectively suppresses MTF2 translation, activating oncogenic pathways that promote OSCC growth. In vitro and in vivo models confirm that PCIF1 knockdown reduces OSCC progression, whereas MTF2 knockdown counteracts this effect, highlighting the importance of the PCIF1-MTF2 axis. Clinical analyses further reveal that high PCIF1 expression and low MTF2 expression correlate with advanced tumour stage, poor treatment response and decreased overall survival. Furthermore, in a preclinical mouse model, PCIF1 knockout enhanced the efficacy of anti-PD1 immunotherapy, reducing tumour burden and improving histological outcomes. Notably, flow cytometry analysis indicated that PCIF1 primarily exerts its effects through tumour-intrinsic mechanisms rather than direct modulation of the immune microenvironment, distinguishing its mode of action from PD1 blockade. These findings establish PCIF1 and MTF2 as promising prognostic markers and therapeutic targets for OSCC, offering new avenues for treatment strategies and patient stratification.</p>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>PCIF1 promotes OSCC progression via m6Am methylation at the MTF2 mRNA 5′ cap.</li>\n \n <li>m6Am methylation suppresses MTF2 translation, enhancing tumour cell proliferation and invasion.</li>\n \n <li>Targeting PCIF1 holds therapeutic potential for OSCC treatment.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 4","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70286","citationCount":"0","resultStr":"{\"title\":\"PCIF1 drives oesophageal squamous cell carcinoma progression via m6Am-mediated suppression of MTF2 translation\",\"authors\":\"Kang Li, Yuxuan Yi, Rongsong Ling, Caihua Zhang, Zhihui Zhang, Yue Wang, Ganping Wang, Jie Chen, Maosheng Cheng, Shuang Chen\",\"doi\":\"10.1002/ctm2.70286\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <p>Oesophageal squamous cell carcinoma (OSCC) represents a highly aggressive malignancy with limited therapeutic options and poor prognosis. This study uncovers PCIF1 as a critical driver of OSCC progression via m6Am RNA modification, leading to translational repression of the tumour suppressor MTF2. Our results demonstrate that PCIF1 selectively suppresses MTF2 translation, activating oncogenic pathways that promote OSCC growth. In vitro and in vivo models confirm that PCIF1 knockdown reduces OSCC progression, whereas MTF2 knockdown counteracts this effect, highlighting the importance of the PCIF1-MTF2 axis. Clinical analyses further reveal that high PCIF1 expression and low MTF2 expression correlate with advanced tumour stage, poor treatment response and decreased overall survival. Furthermore, in a preclinical mouse model, PCIF1 knockout enhanced the efficacy of anti-PD1 immunotherapy, reducing tumour burden and improving histological outcomes. Notably, flow cytometry analysis indicated that PCIF1 primarily exerts its effects through tumour-intrinsic mechanisms rather than direct modulation of the immune microenvironment, distinguishing its mode of action from PD1 blockade. These findings establish PCIF1 and MTF2 as promising prognostic markers and therapeutic targets for OSCC, offering new avenues for treatment strategies and patient stratification.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Key points</h3>\\n \\n <div>\\n <ul>\\n \\n <li>PCIF1 promotes OSCC progression via m6Am methylation at the MTF2 mRNA 5′ cap.</li>\\n \\n <li>m6Am methylation suppresses MTF2 translation, enhancing tumour cell proliferation and invasion.</li>\\n \\n <li>Targeting PCIF1 holds therapeutic potential for OSCC treatment.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":10189,\"journal\":{\"name\":\"Clinical and Translational Medicine\",\"volume\":\"15 4\",\"pages\":\"\"},\"PeriodicalIF\":7.9000,\"publicationDate\":\"2025-03-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70286\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70286\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70286","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
PCIF1 drives oesophageal squamous cell carcinoma progression via m6Am-mediated suppression of MTF2 translation
Oesophageal squamous cell carcinoma (OSCC) represents a highly aggressive malignancy with limited therapeutic options and poor prognosis. This study uncovers PCIF1 as a critical driver of OSCC progression via m6Am RNA modification, leading to translational repression of the tumour suppressor MTF2. Our results demonstrate that PCIF1 selectively suppresses MTF2 translation, activating oncogenic pathways that promote OSCC growth. In vitro and in vivo models confirm that PCIF1 knockdown reduces OSCC progression, whereas MTF2 knockdown counteracts this effect, highlighting the importance of the PCIF1-MTF2 axis. Clinical analyses further reveal that high PCIF1 expression and low MTF2 expression correlate with advanced tumour stage, poor treatment response and decreased overall survival. Furthermore, in a preclinical mouse model, PCIF1 knockout enhanced the efficacy of anti-PD1 immunotherapy, reducing tumour burden and improving histological outcomes. Notably, flow cytometry analysis indicated that PCIF1 primarily exerts its effects through tumour-intrinsic mechanisms rather than direct modulation of the immune microenvironment, distinguishing its mode of action from PD1 blockade. These findings establish PCIF1 and MTF2 as promising prognostic markers and therapeutic targets for OSCC, offering new avenues for treatment strategies and patient stratification.
Key points
PCIF1 promotes OSCC progression via m6Am methylation at the MTF2 mRNA 5′ cap.
期刊介绍：
Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
