Department of Oncology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Fuzhou, 350005, Fujian, China.
Department of Oncology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian, China.
Sci Rep. 2024 Sep 4;14(1):20654. doi: 10.1038/s41598-024-71644-4.
Small cell lung cancer (SCLC) is a very aggressive tumor. Abnormal expression of BUB1 has been reported in several cancer types, wherein it plays a range of functional roles. This work aimed to elucidate the functional significance and molecular impacts of BUB1 in SCLC. It was found that SCLC cell lines exhibited significant BUB1 upregulation relative to control bronchial cells using data from the Gene Expression Omnibus (GEO) database and verified by immunohistochemical staining. BUB1 was also found to promote the proliferative, migratory, invasive activity of SCLC cells, as shown by CCK-8, 3D migration wound-healing, and Transwell assays, as well as flow cytometry. Additionally, it was found that BUB1 silencing enhanced E-cadherin expression while suppressing N-cadherin, Vimentin, ZEB-1, and Snail levels, as shown by Western immunoblotting. The loss of BUB1 also reduced p-AKT and p-mTOR levels without altering total AKT or mTOR protein levels. In conclusion, BUB1 functions as an oncogenic promoter in SCLC, potentially regulating the epithelial-mesenchymal transition by activation of AKT/mTOR signaling.
小细胞肺癌（SCLC）是一种非常侵袭性的肿瘤。据报道，BUB1 在几种癌症类型中表达异常，在这些癌症中，它发挥着多种功能作用。本研究旨在阐明 BUB1 在 SCLC 中的功能意义和分子影响。通过基因表达综合数据库（GEO）数据库的数据和免疫组织化学染色验证，发现 SCLC 细胞系相对于对照支气管细胞表现出显著的 BUB1 上调。CCK-8、3D 迁移划痕愈合和 Transwell 测定以及流式细胞术显示，BUB1 还促进了 SCLC 细胞的增殖、迁移和侵袭活性。此外，Western 免疫印迹显示，BUB1 沉默增强了 E-钙粘蛋白的表达，同时抑制了 N-钙粘蛋白、波形蛋白、ZEB-1 和 Slug 的水平。BUB1 的缺失还降低了 p-AKT 和 p-mTOR 水平，而不改变总 AKT 或 mTOR 蛋白水平。总之，BUB1 在 SCLC 中作为致癌促进剂发挥作用，可能通过激活 AKT/mTOR 信号通路调节上皮-间充质转化。
