Ju Li, Hao Cheng, Yong Zhao, Yunkang Wang, Chen Gong, Renguo Gong, Yan Li
{"title":"ZNF331 通过协同抑制因子 TRIM28 抑制头颈部鳞状细胞癌的增殖","authors":"Ju Li, Hao Cheng, Yong Zhao, Yunkang Wang, Chen Gong, Renguo Gong, Yan Li","doi":"10.1111/odi.15209","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore the regulatory effect of Zinc Finger Protein 331 (ZNF331), a KRAB domain-containing transcriptional repressor, in Head and Neck Squamous Cell Carcinoma (HNSCC).</p><p><strong>Materials and methods: </strong>Data from The Cancer Genome Atlas (TCGA)-HNSC were analyzed. The roles of ZNF331 in HNSCC cell proliferation, cell cycle progression, and its interacting proteins were explored through in vitro manipulation of ZNF331 expression and in vivo xenograft experiments. The epigenetic mechanisms underlying ZNF331 dysregulation were investigated by assessing its promoter methylation and the effects of DNA methyltransferase (DNMT) knockdown.</p><p><strong>Results: </strong>Patients with higher ZNF331 expression had a significantly improved progression-free interval (PFI). ZNF331 overexpression inhibits HNSCC cell proliferation and induces G2/M arrest, while its knockdown enhances oncogenic features. ZNF331 can downregulate the expression of oncogenes such as DDX5, EIF5A, and SET. ZNF331's tumor-suppressive activity requires TRIM28, a universal co-repressor of KRAB-ZNF proteins. ZNF331 expression is suppressed by DNMT3B-mediated promoter hypermethylation. Selective knockdown of DNMT3B, but not DNMT3A, restored ZNF331 expression.</p><p><strong>Conclusions: </strong>ZNF331 acts as a potential tumor suppressor in HNSCC, whose inactivation through DNMT3B-mediated hypermethylation may contribute to HNSCC tumorigenesis. Restoring ZNF331 expression through targeted epigenetic therapies may offer a novel strategy for the treatment of HNSCC.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ZNF331 Represses the Proliferation of Head and Neck Squamous Cell Carcinoma via Co-Repressor TRIM28.\",\"authors\":\"Ju Li, Hao Cheng, Yong Zhao, Yunkang Wang, Chen Gong, Renguo Gong, Yan Li\",\"doi\":\"10.1111/odi.15209\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>This study aims to explore the regulatory effect of Zinc Finger Protein 331 (ZNF331), a KRAB domain-containing transcriptional repressor, in Head and Neck Squamous Cell Carcinoma (HNSCC).</p><p><strong>Materials and methods: </strong>Data from The Cancer Genome Atlas (TCGA)-HNSC were analyzed. The roles of ZNF331 in HNSCC cell proliferation, cell cycle progression, and its interacting proteins were explored through in vitro manipulation of ZNF331 expression and in vivo xenograft experiments. The epigenetic mechanisms underlying ZNF331 dysregulation were investigated by assessing its promoter methylation and the effects of DNA methyltransferase (DNMT) knockdown.</p><p><strong>Results: </strong>Patients with higher ZNF331 expression had a significantly improved progression-free interval (PFI). ZNF331 overexpression inhibits HNSCC cell proliferation and induces G2/M arrest, while its knockdown enhances oncogenic features. ZNF331 can downregulate the expression of oncogenes such as DDX5, EIF5A, and SET. ZNF331's tumor-suppressive activity requires TRIM28, a universal co-repressor of KRAB-ZNF proteins. ZNF331 expression is suppressed by DNMT3B-mediated promoter hypermethylation. Selective knockdown of DNMT3B, but not DNMT3A, restored ZNF331 expression.</p><p><strong>Conclusions: </strong>ZNF331 acts as a potential tumor suppressor in HNSCC, whose inactivation through DNMT3B-mediated hypermethylation may contribute to HNSCC tumorigenesis. Restoring ZNF331 expression through targeted epigenetic therapies may offer a novel strategy for the treatment of HNSCC.</p>\",\"PeriodicalId\":19615,\"journal\":{\"name\":\"Oral diseases\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-11-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/odi.15209\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/odi.15209","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
ZNF331 Represses the Proliferation of Head and Neck Squamous Cell Carcinoma via Co-Repressor TRIM28.
Objective: This study aims to explore the regulatory effect of Zinc Finger Protein 331 (ZNF331), a KRAB domain-containing transcriptional repressor, in Head and Neck Squamous Cell Carcinoma (HNSCC).
Materials and methods: Data from The Cancer Genome Atlas (TCGA)-HNSC were analyzed. The roles of ZNF331 in HNSCC cell proliferation, cell cycle progression, and its interacting proteins were explored through in vitro manipulation of ZNF331 expression and in vivo xenograft experiments. The epigenetic mechanisms underlying ZNF331 dysregulation were investigated by assessing its promoter methylation and the effects of DNA methyltransferase (DNMT) knockdown.
Results: Patients with higher ZNF331 expression had a significantly improved progression-free interval (PFI). ZNF331 overexpression inhibits HNSCC cell proliferation and induces G2/M arrest, while its knockdown enhances oncogenic features. ZNF331 can downregulate the expression of oncogenes such as DDX5, EIF5A, and SET. ZNF331's tumor-suppressive activity requires TRIM28, a universal co-repressor of KRAB-ZNF proteins. ZNF331 expression is suppressed by DNMT3B-mediated promoter hypermethylation. Selective knockdown of DNMT3B, but not DNMT3A, restored ZNF331 expression.
Conclusions: ZNF331 acts as a potential tumor suppressor in HNSCC, whose inactivation through DNMT3B-mediated hypermethylation may contribute to HNSCC tumorigenesis. Restoring ZNF331 expression through targeted epigenetic therapies may offer a novel strategy for the treatment of HNSCC.
期刊介绍：
Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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