General Hospital of Northern Theater Command Base, Jinzhou Medical University, Jinzhou, China.
Eur Rev Med Pharmacol Sci. 2020 Jan;24(2):749-757. doi: 10.26355/eurrev_202001_20055.
The aim of this study was to investigate the expression level of circ-DONSON in glioma and to explore its effect on glioma metastasis and the underlying mechanism.
Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine circ-DONSON expression in 40 paired glioma tumor tissues and adjacent tissues. Meanwhile, the relation between circ-DONSON level and clinical parameters of glioma and the prognosis of patients was analyzed. The expression of circ-DONSON in glioma cell lines was analyzed by qRT-PCR as well. In addition, circs-DONSON silencing model was constructed in glioma cell lines. Cell counting kit-8 (CCK-8), cell scratch, and transwell migration assays were performed to investigate the effect of circ-DONSON on biological functions of glioma cells. Finally, the interplay between FOXO3 and circ-DONSON was explored.
QRT-PCR results revealed that the expression level of circ-DONSON in glioma tumor tissues was remarkably higher than that of adjacent tissues, and the difference was statistically significant (p<0.05). Compared with patients with low expression of circ-DONSON, significantly higher prevalence of lymph node or distant metastasis and worse prognosis were observed in patients with high expression of circ-DONSON (p<0.05). The proliferation and migration abilities of glioma cells in circ-DONSON silenced group were remarkably suppressed when compared with NC group (p<0.05). Additionally, FOXO3 expression was remarkably down-regulated in glioma cell lines and tissues. FOXO3 expression was negatively correlated with circ-DONSON expression. In addition, cell reverse experiment demonstrated that circ-DONSON and FOXO3 can regulate each other, thereby together affecting the malignant progression of glioma.
Circ-DONSON was remarkably associated with lymph node or distant metastasis, as well as poor prognosis of patients with glioma. Furthermore, it promoted the metastasis of glioma cells via regulating FOXO3.
本研究旨在探讨环状 RNA（circ-DONSON）在脑胶质瘤中的表达水平及其对脑胶质瘤转移的影响及其潜在机制。
采用实时荧光定量聚合酶链反应（qRT-PCR）检测 40 对脑胶质瘤组织及其配对癌旁组织中 circ-DONSON 的表达情况。同时分析 circ-DONSON 水平与脑胶质瘤临床参数及患者预后的关系。采用 qRT-PCR 分析 circ-DONSON 在脑胶质瘤细胞系中的表达情况。此外，构建 circ-DONSON 沉默的脑胶质瘤细胞系模型。采用细胞计数试剂盒-8（CCK-8）、细胞划痕和 Transwell 迁移实验检测 circ-DONSON 对脑胶质瘤细胞生物学功能的影响。最后，探讨 FOXO3 与 circ-DONSON 之间的相互作用。
qRT-PCR 结果显示，脑胶质瘤组织中 circ-DONSON 的表达水平明显高于癌旁组织，差异具有统计学意义（p<0.05）。与 circ-DONSON 低表达的患者相比，circ-DONSON 高表达的患者淋巴结或远处转移的发生率明显较高，预后较差（p<0.05）。与 NC 组相比，circ-DONSON 沉默组的胶质瘤细胞增殖和迁移能力明显受到抑制（p<0.05）。此外，在脑胶质瘤细胞系和组织中，FOXO3 的表达明显下调。FOXO3 的表达与 circ-DONSON 的表达呈负相关。此外，细胞反向实验表明，circ-DONSON 和 FOXO3 可以相互调节，从而共同影响脑胶质瘤的恶性进展。
circ-DONSON 与脑胶质瘤患者的淋巴结或远处转移及不良预后密切相关。此外，circ-DONSON 通过调节 FOXO3 促进脑胶质瘤细胞的转移。
