Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Anticancer Drugs. 2023 Aug 1;34(7):866-876. doi: 10.1097/CAD.0000000000001477. Epub 2022 Dec 23.
Lung cancer (LC) is one of the most common malignancies worldwide with low 5-year survival rate. The mechanism of spindle and kinetochore-associated complex subunit 3 (SKA3) in LC tumorgenesis remains largely unclear. The expression of SKA3 in LC cells was detected by quantitative PCR. Cell proliferation, migration and cell cycle were evaluated by functional assays including 5-ethynyl-2'-deoxyuridine, wound healing, transwell assays and flow cytometry analysis. Bioinformatics analysis, chromatin immunoprecipitation, luciferase reporter, co-immunoprecipitation and in vitro phosphorylation assays were applied to explore the interactions between zinc finger E-box binding homeobox 1 (ZEB1) and SKA3/polo-like kinase 1 (PLK1). SKA3 is highly expressed in LC cell lines and drives LC cell proliferation, migration and cell cycle. PLK1 also enhances the malignancy of LC cells. PLK1 can mediate SKA3 phosphorylation and enhance the stability of SKA3 protein, thus promoting LC progression. Besides, we found that transcription factor ZEB1 transcriptionally activates SKA3/PLK1 expression, contributing to LC cell malignancy. This study demonstrated that transcription factor ZEB1 modulates PLK1-mediated SKA3 phosphorylation to accelerate LC cell growth, migration and cycle, which might offer novel insight into LC treatment.
肺癌（LC）是全球最常见的恶性肿瘤之一，5 年生存率低。纺锤体和着丝粒相关复合物亚基 3（SKA3）在 LC 肿瘤发生中的作用机制在很大程度上尚不清楚。通过定量 PCR 检测 LC 细胞中 SKA3 的表达。通过包括 5-乙炔基-2'-脱氧尿苷、划痕愈合、Transwell 测定和流式细胞术分析在内的功能测定评估细胞增殖、迁移和细胞周期。应用生物信息学分析、染色质免疫沉淀、荧光素酶报告基因、共免疫沉淀和体外磷酸化测定来探索锌指 E 盒结合同源盒 1（ZEB1）与 SKA3/丝氨酸苏氨酸激酶 1（PLK1）之间的相互作用。SKA3 在 LC 细胞系中高表达，并驱动 LC 细胞增殖、迁移和细胞周期。PLK1 也增强了 LC 细胞的恶性程度。PLK1 可以介导 SKA3 的磷酸化并增强 SKA3 蛋白的稳定性，从而促进 LC 的进展。此外，我们发现转录因子 ZEB1 转录激活 SKA3/PLK1 的表达，促进 LC 细胞的恶性程度。这项研究表明，转录因子 ZEB1 调节 PLK1 介导的 SKA3 磷酸化，从而加速 LC 细胞的生长、迁移和周期，这可能为 LC 的治疗提供新的思路。
