Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Department of Gynecology and Obstetrics, Lianyungang Meternal and Child Health Hospital, Lianyungang, Jiangsu, China.
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Exp Cell Res. 2023 Sep 1;430(1):113719. doi: 10.1016/j.yexcr.2023.113719. Epub 2023 Jul 12.
Cervical cancer is one of the recognized malignant tumors of female reproductive system. At present, the research and development of biomarkers has attracted increasing attention, and the wide application of clinical cervical cancer screening strategies has significantly reduced its morbidity and mortality. A member of the F-box protein family, FBXO22, is involved in cell cycle, DNA damage repair and many other processes. Dysregulation of FBXO22 plays an important role in the occurrence and development of various tumors, including ovarian cancer, liver cancer and lung cancer. Nevertheless, the effect of FBXO22 in cervical cancer needs further investigation. We found that FBXO22 inhibited cervical cancer cell proliferation, migration and invasion. The results of proteomics studies suggested FBXO22 appears to target the Cyclin G Associated Kinase (GAK) for degradation. The combined results of analysis of cultured cells with altered abundance of FBXO22 by depletion or over-expression in the presence or absence of proteasomal inhibitor, comparison of protein decay rate, as well as cellular ubiquitination, support a hypothesis that FBXO22 mediates the ubiquitin-dependent degradation of GAK. Taken together, our data suggest that FBXO22 has a protective role in cervical cancer.
宫颈癌是女性生殖系统公认的恶性肿瘤之一。目前，生物标志物的研究和开发引起了越来越多的关注，临床宫颈癌筛查策略的广泛应用显著降低了其发病率和死亡率。F-box 蛋白家族的一员 FBXO22 参与细胞周期、DNA 损伤修复和许多其他过程。FBXO22 的失调在包括卵巢癌、肝癌和肺癌在内的各种肿瘤的发生和发展中起着重要作用。然而，FBXO22 在宫颈癌中的作用需要进一步研究。我们发现 FBXO22 抑制了宫颈癌细胞的增殖、迁移和侵袭。蛋白质组学研究的结果表明，FBXO22 似乎将 Cyclin G Associated Kinase（GAK）作为靶标进行降解。在存在或不存在蛋白酶体抑制剂的情况下，通过耗尽或过表达改变 FBXO22 丰度的培养细胞的分析结果、蛋白质衰减率的比较以及细胞内泛素化的综合结果支持 FBXO22 介导 GAK 的泛素依赖性降解的假说。总之，我们的数据表明 FBXO22 在宫颈癌中具有保护作用。
