UHRF1在恶性肿瘤发生和发展中的作用及其靶向治疗的研究进展

The role of UHRF1 in the occurrence and development of malignancies and the advancement of UHRF1-based targeted therapy

泛素样含PHD和环指域1(ubiquitin-like with PHD and ring finger domains 1,UHRF1)在多种肿瘤细胞中高表达,被认为是普遍的肿瘤标志物,其与肿瘤的发生和发展密切相关。在肿瘤细胞中,UHRF1通过调控细胞周期和DNA修复,以及DNA甲基化修饰沉默抑癌基因等途径促进肿瘤细胞的增殖和转移。UHRF1共有5个结构域(SRA、TTD、PHD、RING和UBL),各个结构域都具有重要功能,因此靶向UHRF1的不同结构域开发新型临床治疗方案具备相当的潜力。目前,靶向SRA结构域的潜在抑制剂已报道有NSC232003和UM63,靶向TTD结构的潜在抑制剂已报道有BPC、NV01、2,4-二甲基砒啶和小檗碱,另有多种天然化合物也能够下调UHRF1的水平。因此,本文将就UHRF1的结构与功能、UHRF1参与肿瘤的发生和发展及其靶向治疗中的研究进展作一综述,以期推动靶向UHRF1的新型肿瘤治疗的研发。

UHRF1(ubiquitin-like with PHD and ring finger domains 1)is highly expressed in a variety of tumor cells,considered as a universal tumor marker related to the occurrence and development of tumors.In tumors,UHRF1 promotes the proliferation and metastasis of tumor cellss by regulating the cell cycle and DNA repair,as well as silencing tumor suppressor genes by DNA methylation modification.UHRF1 has 5 domains(SRA,TTD,PHD,RING and,UBL)and each domain has significant functions.Therefore,targeting different domains of UHRF1 is considered as a potential new clinical treatment strategy.Until now,NSC232003 and UM63 have been reported as potential inhibitors to targeting the SRA domain,while BPC,NV01,2,4-lutidine and berberine have been reported as potential inhibitors to targeting the TTD domain of UHRF1.There are also several natural compounds that can down-regulate the level of UHRF1.Therefore,in order to promote the research and development of UHRF1-based targeted therapy,,this review will introduce the structure and function of UHRF1,UHRF1's roles in the occurrence and development of tumors and the current advancement in the corresponding targeted therapy.