[摘 要] 目的：探讨环状RNA hsa_circ_0046701在胶质瘤组织中的表达及其对胶质瘤U251细胞增殖、迁移与侵袭的影响。 方法：收集2022年6月至2023年3月期间在同济大学附属普陀人民医院接受手术治疗的52例胶质瘤患者的瘤组织标本及临床 资料，另收集30例正常脑组织标本作为对照。通过qPCR法检测胶质瘤组织中hsa_circ_0046701表达水平，分析其与患者临床特 征间的关系，通过Kaplan-Meier法分析hsa_circ_0046701水平与生存预后的关系。利用RNA干扰技术，分别将circ_0046701过表 达及空载体（vector）、siRNA-circ_0046701及阴性对照（si-NC）质粒转染到胶质瘤U251细胞中，实验分为si-circ_0046701组、si-NC 组、circ_0046701 OE组、Vector组。应用CCK-8法、Transwell 小室实验检测各组细胞的增殖、迁移及侵袭能力，WB法检测 各组细胞中vimentin、Snail、E-cadherin和cyclin D1蛋白的表达。结果：胶质瘤组织中hsa_circ_0046701表达显著高于正常脑组 织（P < 0.01）。hsa_circ_0046701高表达组患者WHO脑胶质瘤分级（Ⅲ~Ⅳ级）占比显著高于低表达组（P < 0.01），其高表达组患 者术后生存期显著短于低表达组。与si-NC组相比，si-circ_0046701组U251细胞的增殖能力显著降低（P < 0.05或P < 0.01）、迁移 及侵袭细胞数均显著减少（均P < 0.01），细胞中vimentin、Snail、cyclin D1蛋白表达均明显降低（均P < 0.01）、E-cadherin蛋白表达 明显增高（P < 0.01）；与Vector组相比，circ_0046701 OE组U251细胞的增殖能力显著升高（P < 0.01）、迁移及侵袭细胞数均显著 增多（均P < 0.01），细胞中vimentin、Snail、cyclin D1蛋白表达均显著增高（均P < 0.01）、E-cadherin蛋白表达明显降低（P < 0.01）。 结论：环状RNA hsa_circ_0046701在胶质瘤组织中呈高表达，并与患者的不良预后密切相关；敲低hsa_circ_0046701表达能够抑 制脑胶质瘤U251细胞的增殖、迁移及侵袭能力。

[Abstract] Objective: To investigate the expression of circular RNA hsa_circ_0046701 in glioma tissues and its effect on the proliferation, migration and invasion of glioma U251 cells. Methods: Tumor tissue specimens and clinical data of fifty-two glioma patients treated surgically in Putuo People's Hospital Affiliated to Tongji University between June 2022 and March 2023 were collected, and another 30 normal brain tissue specimens were collected as controls. The expression level of hsa_circ_0046701 in glioma tissues was detected by qPCR to analyze the relationship between the level and clinical characteristics of the patient. Kaplan-Meier method was used to analyze the relationship between hsa_circ_0046701 level and survival prognosis. Using RNA interference technology, circ_0046701 overexpression and empty vector, siRNA-circ_0046701 and negative control (si-NC) plasmid were transfected into glioma U251 cells, respectively. The experiment cells were divided into the circ 0046701 OE group, Vector group, si-circ_0046701 group and si-NC group. CCK-8 method and Transwell assay were applied to detect the proliferation, migration and invasion abilities of cells in each group. Western blotting was applied to detect the expressions of vimentin, Snail, E-cadherin and cyclin D1 proteins in cells of each group. Results: The expression level of hsa_circ_0046701 in glioma tissues was significantly higher than that in normal brain tissues (P < 0.01). The percentage of patients with WHO glioma grading (grades Ⅲ~Ⅳ) in the hsa_circ_0046701 high-expression group was significantly higher than that of the hsa_circ_0046701 low expression group (P < 0.01). The OS of patients in the high expression group was significantly shorter than that of the low-expression group. Compared with those in the si-NC group, the proliferation ability of U251 cells in the si-circ_0046701 group was significantly reduced (P < 0.05 or P < 0.01), and the numbers of migrated and invaded cells decreased significantly (both P < 0.01). The expressions of vimentin, Snail, and cyclin D1 proteins in the cells was significantly reduced (all P < 0.01), while the expression of E-cadherin protein increased significantly (P < 0.01). Compared with those in the Vector group, the proliferation ability of U251cells in the circ_0046701 OE group increased significantly (P < 0.01); the numbers of migrated and invaded cells increased significantly (both P < 0.01); the expressions of vimentin, Snail, and cyclin D1 proteins in the cells increaseds significantly (all P < 0.01), and the expression of E-cadherin protein decreased significantly (P < 0.01). Conclusion: Circular RNA hsa_circ_0046701 is highly expressed in glioma tissues, and is correlated with poor patient prognosis. Knockdown of hsa_circ_0046701 expression could inhibit the proliferation, migration and invasion of glioma U251cells.

上海市普陀区人民医院院级科研项目（No. 2023rmky04）