Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
J Cell Biochem. 2020 Jan;121(1):690-697. doi: 10.1002/jcb.29315. Epub 2019 Aug 12.
Glioma (GM) is a highly lethal human cancer. Circular RNAs (circRNAs) act as an imperative factor in oncogenesis. We aimed to investigate the biological functions and mechanisms of circ-CDC45 in GM. circ-CDC45 expression in GM specimens and cell lines was measured by real-time quantitative reverse transcription polymerase chain reaction. Fisher's exact test and Kaplan-Meier curves further analyzed its clinical implications. A gain/loss-of-function study was conducted to investigate the role of circ-CDC45 in GM. Additionally, luciferase reporter and rescue assays were performed to unravel the mechanisms of circ-CDC45. High circ-CDC45 expression was found in GM specimens and cells, which was tightly related to a larger tumor size, higher world health organization (WHO) stages, and worse survival for patients with GM. Functionally, manipulation of circ-CDC45 expression strongly affected cell growth, apoptosis, migration and invasion, which suggests the oncogenic function of circ-CDC45 in GM oncogenesis. Stepwise mechanism studies indicated that circ-CDC45 sponged and regulated the expression of miR-516b and miR-527 to promote cell growth and invasion. Briefly, the regulatory network of circ-CDC45/miR-516b/miR-527 plays a pivotal role in GM tumorigenesis and may act as a potential target for GM treatment.
神经胶质瘤（GM）是一种高度致命的人类癌症。环状 RNA（circRNA）在肿瘤发生中起着重要作用。我们旨在研究 circ-CDC45 在 GM 中的生物学功能和机制。通过实时定量逆转录聚合酶链反应测量 GM 标本和细胞系中的 circ-CDC45 表达。Fisher 确切检验和 Kaplan-Meier 曲线进一步分析了其临床意义。进行了增益/损耗功能研究，以研究 circ-CDC45 在 GM 中的作用。此外，还进行了荧光素酶报告和挽救测定，以揭示 circ-CDC45 的作用机制。在 GM 标本和细胞中发现高 circ-CDC45 表达，与更大的肿瘤大小、更高的世界卫生组织（WHO）分期以及 GM 患者的预后较差密切相关。功能上，circ-CDC45 表达的操纵强烈影响细胞生长、凋亡、迁移和侵袭，表明 circ-CDC45 在 GM 肿瘤发生中的致癌功能。逐步机制研究表明，circ-CDC45 可吸附和调节 miR-516b 和 miR-527 的表达，从而促进细胞生长和侵袭。简而言之，circ-CDC45/miR-516b/miR-527 的调控网络在 GM 肿瘤发生中起着关键作用，可能成为 GM 治疗的潜在靶点。
