锌指蛋白在口腔癌发生发展中的作用研究进展  

Research progress on the role of zinc finger proteins in the development of oral cancer

作　　者：斯航 冯燕 余丽 SI Hang;FENG Yan;YU Li(Department of Pediatric Dentistry,The Affiliated Stomatology Hospital,Southwest Medical University,Luzhou 646000,China;School of Stomatology,Southwest Medical University,Luzhou 646000,China;Luzhou Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Southwest Medical University,Luzhou 646000,China;Department of Periodontal Mucosal Disease,The Affiliated Stomatology Hospital,Southwest Medical University,Luzhou 646000,China;NHC Key Laboratory of Nuclear Technology Medical Transformation(Mianyang Central Hospital),Mianyang 621000,China)

机构地区：[1]西南医科大学附属口腔医院儿童口腔科,四川泸州646000 [2]西南医科大学口腔医学院,四川泸州646000 [3]西南医科大学口颌面修复重建和再生泸州市重点实验室,四川泸州646000 [4]西南医科大学附属口腔医院牙周黏膜病科,四川泸州646000 [5]国家卫生健康委核技术医学转化实验室(绵阳市中心医院),四川绵阳621000

出　　处：《口腔疾病防治》2025年第5期425-432,共8页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：国家自然科学基金项目(82403404);四川省科学技术厅科技计划项目(2024JDRC0040);四川省医学青年创新课题计划(Q23028);国家卫生健康委核技术医学转化重点实验室开放课题(2023HYX028)。

摘　　要：口腔癌是头颈部最常见的恶性肿瘤之一,治疗效果常欠佳。锌指蛋白(zinc finger proteins,ZNFs)是人类基因组中最大的转录因子家族蛋白之一,通过锌离子折叠形成独特的三维结构,能够与DNA、RNA及蛋白质结合,调控转录、RNA包装、蛋白质折叠等生物学过程。近年来,关于ZNFs参与调控口腔癌进展的功能机制研究日益增多。目前已报道的ZNFs包括:①调控肿瘤细胞侵袭转移的ZNF677、ZNF460、ZNF154和ZNF132、ZNF281、Kaiso、ZNF582;②调控细胞周期的ZNF750和含PEST的核蛋白(PEST-containing nuclear pro-tein,PCNP);③参与肿瘤免疫微环境形成的ZNF71和髓指锌指1(myeloid zinc finger 1,MZF1)。其中,甲基化修饰介导ZNF677在口腔癌中的低表达,ZNF677通过抑制丝氨酸/苏氨酸激酶/叉头盒转录因子O3a(protein kinase B/forkhead box O3a,AKT/FOXO3a)通路减少口腔癌细胞的增殖、迁移和侵袭;ZNF460通过microRNA-320a/X连锁α-地中海贫血精神发育迟滞(alpha thalassemia/mental retardation,X-linked,ATRX)轴促进口腔癌细胞的增殖、迁移和侵袭。此外,ZNF750通过抑制细胞周期转录因子活性抑制口腔癌的生长和转移。而ZNF71可通过减少肿瘤免疫细胞的浸润来促进口腔癌的进展。本文对ZNFs参与口腔癌进展的分子机制、调控关系以及促瘤/抑瘤等方面的研究进展进行综述,以期为口腔癌的诊疗提供新思路。Oral cancer is one of the most common malignancies in the head and neck regions.few patients benefit from current clinical therapy.Zinc finger proteins(ZNFs)are one of the largest transcription factor family proteins in the human genome.ZNFs bind to DNA,RNA,and proteins through their unique three-dimensional structure created by zinc ions to regulate gene transcription,RNA packaging,and protein folding.In recent years,the number of studies focused on the functional mechanism of ZNFs in regulating the progression of oral cancer has been increasing,with focuses on:①ZNF677,ZNF460,ZNF154,ZNF132,ZNF281,Kaiso,and ZNF582,which regulate the invasion and metastasis of tumor cells;②ZNF750 and PEST-containing nuclear protein(PCNP),which regulate the cell cycle;③ZNFs,which are involved in forming the tumor immune microenvironment,such as ZNF71 and myeloid zinc finger 1(MZF1).For example,methylation modification modulates the reduction of ZNF677 in oral cancer and reduces the proliferation,migration,and invasion of oral cancer cells by inhibiting the protein kinase B/forkhead box O3a(AKT/FOXO3a)pathway;and ZNF460 promotes the proliferation,migration,and invasion of oral cancer cells by regulating microRNA-320a/alpha thalassemia/mental retardation,X-linked(ATRX)axis.In addition,ZNF750 inhibits the growth and metastasis of oral cancer by suppressing cell cycle transcription factor activity.Further,ZNF71 promotes the progression of oral cancer by reducing the infiltration of tumor immune cells.In this review,we will summarize the molecular mechanism,regulatory meshwork,and pro-tumor and anti-tumor roles of ZNFs in the pathogenesis of oral cancer.Our study may provide a new strategy for the diagnosis and treatment of oral cancer.

关 键 词：锌指蛋白 口腔癌 肿瘤细胞 肿瘤微环境 肿瘤免疫 肿瘤治疗 

分 类 号：R78[医药卫生—口腔医学]