Abstract Among astrocyte tumors, glioblastoma (GBM) is the most malignant glioma, highly aggressive and invasive, with extremely poor prognosis. Previous research has reported that microRNAs (miRNAs) participate in the progression of many cancers. Thus, this study aimed to explore the role and the underlying mechanisms of microRNA (miR)-489-3p in GBM progression. The expression of miR-489-3p and brain-derived neurotrophic factor (BDNF) mRNA was measured by quantitative real-time polymerase chain reaction. Western blot analysis was used to detect BDNF protein and the PI3K/AKT pathway-related protein. Cell proliferation, apoptosis, migration, and invasion were analyzed using CKK-8 assay, flow cytometry, and transwell assay, respectively. The interaction between BDNF and miR-489-3p was explored by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. MiR-489-3p was down-regulated and BDNF was up-regulated in GBM tissues and cells. MiR-489-3p re-expression or BDNF knockdown inhibited GBM cell proliferation, migration, and invasion, and promoted apoptosis. BDNF was a target of miR-489-3p, and BDNF up-regulation reversed the effects of miR-489-3p on GBM cells. The protein levels of p-AKT and p-PI3K were notably reduced in GBM cells by overexpression of miR-489-3p, but were rescued following BDNF up-regulation. Therefore, miR-489-3p inhibited proliferation, migration, and invasion, and induced apoptosis, by targeting the BDNF-mediated PI3K/AKT pathway in GBM, providing new strategies for clinical treatment of GBM.

中文翻译：

---

MiR-489-3p 通过靶向胶质母细胞瘤中 BDNF 介导的 PI3K/AKT 通路，抑制细胞增殖、迁移和侵袭，并诱导细胞凋亡

摘要 星形胶质细胞瘤中，胶质母细胞瘤（GBM）是恶性程度最高的胶质瘤，具有高度侵袭性和侵袭性，预后极差。此前的研究表明，microRNA (miRNA) 参与了许多癌症的进展。因此，本研究旨在探讨微小RNA（miR）-489-3p在GBM进展中的作用和潜在机制。通过实时定量聚合酶链反应测量 miR-489-3p 和脑源性神经营养因子 (BDNF) mRNA 的表达。Western blot分析检测BDNF蛋白和PI3K/AKT通路相关蛋白。分别使用CKK-8测定、流式细胞术和transwell测定分析细胞增殖、凋亡、迁移和侵袭。通过荧光素酶报告基因测定和 RNA 免疫沉淀 (RIP) 测定探索 BDNF 和 miR-489-3p 之间的相互作用。GBM 组织和细胞中 MiR-489-3p 下调，BDNF 上调。MiR-489-3p重新表达或BDNF敲低可抑制GBM细胞增殖、迁移和侵袭，并促进细胞凋亡。BDNF 是 miR-489-3p 的靶标，BDNF 上调可逆转 miR-489-3p 对 GBM 细胞的影响。GBM 细胞中 p-AKT 和 p-PI3K 的蛋白水平因 miR-489-3p 的过表达而显着降低，但在 BDNF 上调后得到恢复。因此，miR-489-3p通过靶向GBM中BDNF介导的PI3K/AKT通路，抑制增殖、迁移和侵袭，并诱导细胞凋亡，为GBM的临床治疗提供新策略。