Department of Geriatrics, Jinan Zhangqiu District Hospital of TCM, Jinan, 250200, China.
Department of Public Health, Jinan Zhangqiu District Hospital of TCM, Jinan, 250200, China.
World J Surg Oncol. 2020 Jun 30;18(1):147. doi: 10.1186/s12957-020-01927-3.
Mounting evidences displayed that miRNAs play crucial roles in tumor initiation and development. However, the regulation and relevant mechanism of miR-1825 in glioblastoma (GBM) remain unclear.
qRT-PCR was used to detect miR-1825 and CDK14 mRNA expression. Western blot was applied for testing protein levels (VEGF, E-cadherin, N-cadherin, vimentin, β-catenin, c-myc, p-c-Jun). MTT and transwell assays were used for detecting GBM cell progression, including cell viability, migration, and invasion.
The results showed that miR-1825 was decreased in GBM tissue specimens by qRT-PCR and it was confirmed as a prognostic marker of GBM by Kaplan-Meier survival analysis. Moreover, we also found that miR-1825 upregulation suppressed GBM cell viability, tumor growth, invasion, and migration. Furthermore, CDK14 was first identified as the direct target of miR-1825 by Luciferase reporter assay. CDK14 acted as an oncogene in GBM development by immunohistochemistry. In addition, Western blot analysis demonstrated that miR-1825 regulated Wnt/β-catenin signaling pathway in GBM development.
In conclusion, miR-1825 upregulation suppressed GBM progression by targeting CDK14 through Wnt/β-catenin pathway.
越来越多的证据表明 miRNA 在肿瘤的发生和发展中起着至关重要的作用。然而,miR-1825 在胶质母细胞瘤(GBM)中的调控及其相关机制仍不清楚。
采用 qRT-PCR 检测 miR-1825 和 CDK14 mRNA 表达。Western blot 检测蛋白水平(VEGF、E-钙黏蛋白、N-钙黏蛋白、波形蛋白、β-连环蛋白、c-myc、p-c-Jun)。MTT 和 Transwell 检测用于检测 GBM 细胞的进展,包括细胞活力、迁移和侵袭。
qRT-PCR 显示 miR-1825 在 GBM 组织标本中降低,并通过 Kaplan-Meier 生存分析证实其为 GBM 的预后标志物。此外,我们还发现 miR-1825 的上调抑制了 GBM 细胞的活力、肿瘤生长、侵袭和迁移。此外,通过荧光素酶报告基因检测首次鉴定出 CDK14 是 miR-1825 的直接靶标。免疫组织化学显示 CDK14 在 GBM 发展中作为癌基因。此外,Western blot 分析表明 miR-1825 通过 Wnt/β-catenin 信号通路调节 GBM 的发展。
总之,miR-1825 通过 Wnt/β-catenin 通路靶向 CDK14 抑制 GBM 的进展。