Department of Gynecology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi China.
Department of General Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi China.
Bioengineered. 2021 Dec;12(1):5759-5768. doi: 10.1080/21655979.2021.1968778.
There is growing evidence that threonine tyrosine kinase (TTK) dysregulation is linked to the progression of multiple malignancies. Nonetheless, the role of TTK in ovarian cancer (OC) remains unclear. The GEO2R method was employed to screen out the mRNAs that were abnormally expressed between OC tissues and normal ovarian tissues using three datasets from the Gene Expression Omnibus (GEO) database: GSE14407, GSE18520, and GSE36668. Moreover, the Kaplan-Meier plotter was utilized to investigate the association between TTK expression and OC patients' prognosis. Furthermore, quantitative real-time PCR (qRT-PCR) was applied to examine miR-582-5p expression and TTK mRNA expression in OC tissues and cells. Additionally, immunohistochemistry (IHC) experiment and Western blot were executed to examine TTK protein expression in OC tissues and cells, respectively. In addition, Cell Counting Kit-8 (CCK-8), transwell, and flow-cytometry experiments were performed to examine the multiplication, migration, and apoptosis of OC cells, respectively. In addition, dual-luciferase reporter gene tests were executed to validate the targeting relationship between miR-582-5p and TTK. We demonstrated that TTK expression was up-regulated in OC tissues and cells, and its overexpression was found to be associated with an adverse prognosis in OC patients. TTK overexpression enhanced OC cell multiplication and migration, and repressed apoptosis. Mechanistically, TTK was a downstream target of miR-582-5p. Furthermore, miR-582-5p overexpression impeded OC cell multiplication and migration, while TTK overexpression reversed this phenomenon. These data suggest that miR-582-5p and TTK are promising targets for OC diagnosis and therapy.
越来越多的证据表明，苏氨酸酪氨酸激酶（TTK）失调与多种恶性肿瘤的进展有关。然而，TTK 在卵巢癌（OC）中的作用仍不清楚。本研究采用 GEO2R 方法，从基因表达综合数据库（GEO）中筛选出三个数据集（GSE14407、GSE18520 和 GSE36668）中 OC 组织与正常卵巢组织之间异常表达的 mRNAs。此外，Kaplan-Meier plotter 用于研究 TTK 表达与 OC 患者预后之间的关系。进一步采用实时荧光定量 PCR（qRT-PCR）检测 OC 组织和细胞中 miR-582-5p 表达和 TTK mRNA 表达。此外，免疫组织化学（IHC）实验和 Western blot 分别用于检测 OC 组织和细胞中 TTK 蛋白表达。此外，细胞计数试剂盒-8（CCK-8）、Transwell 和流式细胞术实验分别用于检测 OC 细胞的增殖、迁移和凋亡。此外，还进行了双荧光素酶报告基因实验以验证 miR-582-5p 与 TTK 之间的靶向关系。结果表明，TTK 在 OC 组织和细胞中表达上调，其过表达与 OC 患者不良预后相关。TTK 过表达促进 OC 细胞增殖和迁移，抑制凋亡。机制上，TTK 是 miR-582-5p 的下游靶基因。此外，miR-582-5p 过表达抑制 OC 细胞增殖和迁移，而 TTK 过表达逆转了这一现象。这些数据表明，miR-582-5p 和 TTK 是 OC 诊断和治疗的有前途的靶点。
