Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
Department of Nephrology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
J Cell Biochem. 2019 Jun;120(6):10391-10401. doi: 10.1002/jcb.28323. Epub 2019 Jan 4.
Forkhead Box M1 (FOXM1) is a member of the forkhead/winged-helix transcription factors regulating proliferation-associated genes and is critical to DNA replication and mitosis. With this said, the function of FOXM1 in renal cell carcinoma (RCC) has not been clearly elucidated. Thus, in this study, the expression pattern of FOXM1 was significantly upregulated in RCC tissues compared with adjacent noncancerous tissues. Moreover, using liquid chromatography with tandem mass spectrometry (LC-MS/MS), FOXM1 can interact with homeodomain interacting protein kinase-2 (HIPK2). In addition, FOXM1 can be phosphorylated by HIPK2. Furthermore, HIPK2 knockdown inhibits FOXM1 phosphorylation and reduces transcription of FOXM1 associated genes: Cyclin B1 and Aurora B. In addition, HIPK2 knockdown hampers the RCC cells cycle progression and suppresses cell viability in vivo and in vitro. In conclusion, the phosphorylation of FOXM1 by HIPK2 can promote FOXM1 transcription activity and cell proliferation in RCC, thus, indicating a potential mechanism for the treatment of human RCC in the future.
叉头框蛋白 M1（FOXM1）是调节增殖相关基因的叉头/翼状螺旋转录因子家族的成员，对 DNA 复制和有丝分裂至关重要。也就是说，FOXM1 在肾细胞癌（RCC）中的功能尚未明确阐明。因此，在这项研究中，与相邻的非癌组织相比，FOXM1 在 RCC 组织中的表达模式明显上调。此外，通过液相色谱-串联质谱（LC-MS/MS），FOXM1 可以与同源域相互作用蛋白激酶-2（HIPK2）相互作用。此外，FOXM1 可以被 HIPK2 磷酸化。此外，HIPK2 敲低抑制 FOXM1 磷酸化并减少与 FOXM1 相关的基因：细胞周期蛋白 B1 和 Aurora B 的转录。此外，HIPK2 敲低阻碍 RCC 细胞周期进程，并在体内和体外抑制细胞活力。总之，HIPK2 对 FOXM1 的磷酸化可以促进 RCC 中 FOXM1 的转录活性和细胞增殖，因此，为未来人类 RCC 的治疗提供了一种潜在的机制。
