Abstract：
Glioblastoma is the most frequent form of malignant brain tumor. Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is overexpressed and involved in the tumorigenesis and metastasis of glioblastoma. miR-130a-3p has been revealed to be aberrantly expressed in tumors and has aroused wide attention. In present study, we would like to investigate the effect and potential mechanism of miR-130a-3p on the proliferation and migration in glioblastoma. The relative expression levels of miR-130a-3p and CPEB4 in glioblastoma cell lines were detected by real-time quantitative polymerase chain reaction. Cell viability and migration were detected by methylthiazolyl tetrazolium assay and transwell assay, and cell cycle analysis was detected by flow cytometry. The expression of CPEB4 protein and epithelial-mesenchymal transition associated markers were detected by western blot. Bioinformatics and luciferase activity analysis were used to verify the targeting relationship between miR-130a-3p and CPEB4. We observed that the expression of CPEB4 was upregulated while that of miR-130a-3p was downregulated in glioblastoma cell lines. CPEB4 was validated as a target of miR-130a-3p by luciferase activity assay. Increased levels of miR-130a-3p inhibited the proliferation and migration of the glioblastoma cells and the overexpression of miR-130a-3p inhibited epithelial-mesenchymal transition. However, CPEB4 overexpression resisted the inhibitory effects of miR-130a-3p. Our study elucidates CPEB4 is upregulated because of the downregulated miR-130a-3p in glioblastoma, which enhances the glioblastoma growth and migration, suggesting a potential therapeutic target for the disease.
摘要：
胶质母细胞瘤是恶性脑肿瘤的最常见形式。细胞质聚腺苷酸化元件结合蛋白4(CPEB4)过表达并参与胶质母细胞瘤的肿瘤发生和转移。miR-130a-3p在肿瘤中异常表达,引起广泛关注。在目前的研究中,我们想探讨miR-130a-3p对胶质母细胞瘤增殖和迁移的影响及其潜在机制。通过实时定量聚合酶链反应检测胶质母细胞瘤细胞系中miR-130a-3p和CPEB4的相对表达水平。通过甲基噻唑基四唑盐测定和transwell测定检测细胞活力和迁移，流式细胞仪检测细胞周期。Westernblot检测CPEB4蛋白和上皮间质转化相关标志物的表达。采用生物信息学和荧光素酶活性分析验证miR-130a-3p与CPEB4的靶向关系。我们观察到胶质母细胞瘤细胞系中CPEB4的表达上调，而miR-130a-3p的表达下调。通过荧光素酶活性测定验证CPEB4作为miR-130a-3p的靶标。miR-130a-3p水平的增加抑制了胶质母细胞瘤细胞的增殖和迁移，miR-130a-3p的过表达抑制了上皮-间质转化。然而,CPEB4过表达抵抗miR-130a-3p的抑制作用。我们的研究表明，由于胶质母细胞瘤中miR-130a-3p的下调，CPEB4上调。促进胶质母细胞瘤的生长和迁移，提示该疾病的潜在治疗目标。
