Zbtb7c(也称为Kr-pok)是一种锌指和BTB结构域包含蛋白,属于POZ/BTB锌指家族,是一种重要的转录因子。Zbtb7c在细胞周期、细胞代谢、细胞增殖和分化等生物学过程中发挥重要作用。Zbtb7c的表达模式具有组织和细胞特异性,其功能涉及多个生物学过程,包括细胞代谢、细胞增殖、细胞分化、细胞凋亡和肿瘤发生等。
Zbtb7c作为转录因子,参与调控多种基因的表达。在细胞代谢方面,Zbtb7c可以与组蛋白去乙酰化酶3(Hdac3)形成复合物,结合胰岛素反应元件(IREs)并激活葡萄糖-6-磷酸酶(G6pc)和磷酸烯醇式丙酮酸羧化酶1(Pck1)的转录,从而在禁食状态下促进糖异生,维持血糖稳态[3]。在细胞增殖方面,Zbtb7c可以与PIAS1相互作用,破坏PIAS1与p-STAT1的结合,从而激活GLS1转录,增加谷氨酰胺摄取,促进肿瘤细胞增殖[4]。在细胞分化方面,Zbtb7c可以与p53相互作用,结合到SIRT1基因的启动子区,抑制SIRT1的表达,进而影响脂质代谢相关基因的表达,如Pgc-1α和Pparγ,导致肥胖的发生[1]。
Zbtb7c的表达模式与多种疾病的发生发展密切相关。在肿瘤发生方面,Zbtb7c的表达水平与肿瘤的发生、发展及预后密切相关。在结直肠癌中,Zbtb7c的表达水平与患者的预后密切相关,低表达Zbtb7c的患者预后较差[2]。在食管癌中,Zbtb7c的表达水平与患者的预后密切相关,低表达Zbtb7c的患者预后较差[5]。在缺血性损伤方面,Zbtb7c的表达水平与缺血性损伤的程度密切相关,Zbtb7c的表达上调与脑梗死体积增大相关[6]。
Zbtb7c在多种疾病中发挥重要作用,包括肿瘤、代谢性疾病和缺血性损伤等。Zbtb7c的表达模式与疾病的发生、发展及预后密切相关,可以作为疾病诊断和预后的潜在生物标志物。此外,Zbtb7c还可以作为潜在的治疗靶点,为疾病的治疗提供新的思路和策略。
参考文献:
1. Choi, Won-Il, Yoon, Jae-Hyun, Choi, Seo-Hyun, Kim, Hail, Hur, Man-Wook. 2021. Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity. In Experimental & molecular medicine, 53, 917-932. doi:10.1038/s12276-021-00628-5. https://pubmed.ncbi.nlm.nih.gov/34017061/
2. Chen, Xuenuo, Jiang, Zhongxiang, Wang, Zhijian, Jiang, Zheng. 2021. The prognostic and immunological effects of ZBTB7C across cancers: friend or foe? In Aging, 13, 12849-12864. doi:10.18632/aging.202955. https://pubmed.ncbi.nlm.nih.gov/33946045/
3. Choi, Won-Il, Yoon, Jae-Hyeon, Song, Ji-Yang, Lee, In-Kyu, Hur, Man-Wook. 2019. Zbtb7c is a critical gluconeogenic transcription factor that induces glucose-6-phosphatase and phosphoenylpyruvate carboxykinase 1 genes expression during mice fasting. In Biochimica et biophysica acta. Gene regulatory mechanisms, 1862, 643-656. doi:10.1016/j.bbagrm.2019.04.001. https://pubmed.ncbi.nlm.nih.gov/30959128/
4. Hur, Man-Wook, Yoon, Jae-Hyeon, Kim, Min-Young, Ko, Hyeonseok, Jeon, Bu-Nam. 2017. Kr-POK (ZBTB7c) regulates cancer cell proliferation through glutamine metabolism. In Biochimica et biophysica acta. Gene regulatory mechanisms, 1860, 829-838. doi:10.1016/j.bbagrm.2017.05.005. https://pubmed.ncbi.nlm.nih.gov/28571744/
5. Song, An-Yi, Mu, Lan, Dai, Xiao-Yong, Wang, Li-Jun, Huang, Lai-Qiang. . Analysis of Significant Genes and Pathways in Esophageal Cancer Based on Gene Expression Omnibus Database. In Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih, 38, 20-28. doi:10.24920/004148. https://pubmed.ncbi.nlm.nih.gov/36855320/
6. Du, Rose, Zhou, Jing, Lorenzano, Svetlana, Paigen, Beverly, Weiss, Scott T. 2015. Integrative Mouse and Human Studies Implicate ANGPT1 and ZBTB7C as Susceptibility Genes to Ischemic Injury. In Stroke, 46, 3514-22. doi:10.1161/STROKEAHA.115.010767. https://pubmed.ncbi.nlm.nih.gov/26542693/