Kcmf1,也称为钾通道调节因子1,是一种锌指蛋白,在多种细胞功能和疾病过程中发挥着重要作用。Kcmf1具有多种生物学功能,包括参与细胞增殖、迁移、侵袭、细胞凋亡和细胞周期调控等。
Kcmf1在多种癌症中发挥重要作用。在口腔鳞状细胞癌(OSCC)中,Kcmf1被认为是超增强子调控的预后生物标志物,其高表达与患者的不良预后相关[3]。在胰腺癌中,Kcmf1的表达上调,并且下调Kcmf1可以抑制胰腺癌的发生发展[7]。在Ewing肉瘤中,Kcmf1的表达水平与CD99的表达水平呈负相关,Kcmf1可能是一种潜在的转移抑制基因[6]。
Kcmf1还参与细胞应激反应的调控。在缺氧和氧化应激条件下,Kcmf1可以与N-末端半胱氨酸残基结合,并参与K63和K27连接的泛素化,从而影响蛋白质的降解和细胞应激反应[5]。此外,Kcmf1还参与泛素化级联反应,调节整合应激反应(ISR)和肿瘤细胞的存活[1][2]。
Kcmf1还与微RNA(miRNA)的调控有关。在妊娠高血压症中,miR-210的表达上调,而Kcmf1的表达下调,提示miR-210可能通过下调Kcmf1的表达参与妊娠高血压症的发生发展[4]。
Kcmf1与14-3-3σ蛋白相互作用,抑制人结肠癌干细胞的增殖和集落形成[8]。14-3-3σ是一种细胞质蛋白,参与多种细胞功能的调控,包括细胞周期、细胞凋亡和信号转导等。
Kcmf1还参与ALK融合蛋白的形成,ALK融合蛋白是非小细胞肺癌(NSCLC)的重要驱动因子[9]。在NSCLC患者中,Kcmf1与ALK融合蛋白形成KCMF1-ALK融合蛋白,KCMF1-ALK融合蛋白的表达与患者的预后相关[9]。
综上所述,Kcmf1是一种重要的锌指蛋白,参与多种细胞功能和疾病过程的调控。Kcmf1在多种癌症中发挥重要作用,包括口腔鳞状细胞癌、胰腺癌和Ewing肉瘤等。Kcmf1还参与细胞应激反应的调控,与miRNA的调控有关,并与14-3-3σ蛋白相互作用,抑制人结肠癌干细胞的增殖和集落形成。此外,Kcmf1还参与ALK融合蛋白的形成,ALK融合蛋白是非小细胞肺癌的重要驱动因子。因此,Kcmf1的研究对于深入理解多种疾病的发生发展机制,以及开发新的治疗策略具有重要意义。
参考文献:
1. Cervia, Lisa D, Shibue, Tsukasa, Borah, Ashir A, Vazquez, Francisca, Hahn, William C. . A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas. In Cancer discovery, 13, 766-795. doi:10.1158/2159-8290.CD-22-1230. https://pubmed.ncbi.nlm.nih.gov/36576405/
2. Leli, Nektaria Maria, Koumenis, Constantinos. . A Novel Ubiquitin Complex Regulates Aneuploid Epithelial Tumors by Moderating an Integrated Stress Response. In Cancer discovery, 13, 535-537. doi:10.1158/2159-8290.CD-22-1440. https://pubmed.ncbi.nlm.nih.gov/36855916/
3. Zhang, Liru, Li, Huanju, Qiu, Yongle, Liu, Xin, Wang, Wenjing. . Screening and cellular validation of prognostic genes regulated by super enhancers in oral squamous cell carcinoma. In Bioengineered, 12, 10073-10088. doi:10.1080/21655979.2021.1997089. https://pubmed.ncbi.nlm.nih.gov/34709988/
4. Luo, Rongcan, Shao, Xuan, Xu, Peng, Peng, Chun, Wang, Yan-Ling. 2014. MicroRNA-210 contributes to preeclampsia by downregulating potassium channel modulatory factor 1. In Hypertension (Dallas, Tex. : 1979), 64, 839-45. doi:10.1161/HYPERTENSIONAHA.114.03530. https://pubmed.ncbi.nlm.nih.gov/24980667/
5. Heo, Ah Jung, Kim, Su Bin, Ji, Chang Hoon, Kim, Bo Yeon, Kwon, Yong Tae. . The N-terminal cysteine is a dual sensor of oxygen and oxidative stress. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2107993118. https://pubmed.ncbi.nlm.nih.gov/34893540/
6. Kreppel, M, Aryee, D N T, Schaefer, K-L, Poremba, C, Kovar, H. . Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells. In Oncogene, 25, 2795-800. doi:. https://pubmed.ncbi.nlm.nih.gov/16314831/
7. Beilke, S, Oswald, F, Genze, F, Adler, G, Wagner, M. 2010. The zinc-finger protein KCMF1 is overexpressed during pancreatic cancer development and downregulation of KCMF1 inhibits pancreatic cancer development in mice. In Oncogene, 29, 4058-67. doi:10.1038/onc.2010.156. https://pubmed.ncbi.nlm.nih.gov/20473331/
8. Zou, Jian, Mi, Lin, Yu, Xiao-Feng, Dong, Jie. . Interaction of 14-3-3σ with KCMF1 suppresses the proliferation and colony formation of human colon cancer stem cells. In World journal of gastroenterology, 19, 3770-80. doi:10.3748/wjg.v19.i24.3770. https://pubmed.ncbi.nlm.nih.gov/23840115/
9. Xia, Wenchao, Yang, Jing, Li, Hongbin, Li, Ling, Liu, Jinfeng. 2024. Comparing Genomic Profiles of ALK Fusion-Positive and ALK Fusion-Negative Nonsmall Cell Lung Cancer Patients. In Global medical genetics, 11, 175-186. doi:10.1055/s-0044-1787301. https://pubmed.ncbi.nlm.nih.gov/38873557/