Glioma is a brain tumor with high morbidity and mortality rates. Understanding its molecular pathogenesis can provide targets and therapeutic strategies for glioma treatment. miR-338-3p represses tumor growth in several cancers, including glioma. Thus, this study aimed to identify the regulatory effects of miR-338-3p/phosphoinositide 3-kinase (PI3K)/Akt/thrombospondins 1 (THBS1) on glioma progression. Quantitative reverse transcription polymerase chain reaction and western blotting were performed to evaluate the levels of miR-338-3p, THBS1, and PI3K/Akt phosphorylation-related proteins. TargetScan software predicted that miR-338-3p targeted THBS1. This was confirmed by performing the dual-luciferase assay. Wound-healing and cell-counting-kit-8 experiments were performed to analyze how THBS1 and miR-338-3p affect the ability of glioma cells to migrate and proliferate. The effect of miR-338-3p on tumorigenicity in mice was also analyzed. miR-338-3p downregulation was observed in gliomas, whereas THBS1 showed the opposite trend. By suppressing the PI3K/Akt signaling pathway activation, miR-338-3p overregulated the ability of glioma cells to migrate and proliferate in vitro. Additionally, miR-338-3p inhibited the development of glioma tumors in vivo. Moreover, miR-338-3p directly targeted THBS1. THBS1 overexpression promoted glioma cell migration and proliferation by increasing PI3K/Akt phosphorylation. Nonetheless, miR-338-3p overregulation alleviated the effects of THBS1 overexpression. The miR-338-3p/PI3K/Akt/THBS1 regulatory axis can modulate the progression of glioma cell proliferation and migration; thus, it can be considered a therapeutic biomarker.

中文翻译：

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Mir-338-3p 靶向 THBS1 通过抑制 PI3K/Akt 通路来减弱神经胶质瘤进展

胶质瘤是一种发病率和死亡率很高的脑肿瘤。了解其分子发病机制可以为神经胶质瘤的治疗提供靶点和治疗策略。miR-338-3p 抑制多种癌症的肿瘤生长，包括神经胶质瘤。因此，本研究旨在确定 miR-338-3p/磷酸肌醇 3-激酶 (PI3K)/Akt/血小板反应蛋白 1 (THBS1) 对神经胶质瘤进展的调节作用。进行定量逆转录聚合酶链反应和蛋白质印迹来评估 miR-338-3p、THBS1 和 PI3K/Akt 磷酸化相关蛋白的水平。TargetScan 软件预测 miR-338-3p 靶向 THBS1。通过进行双荧光素酶测定证实了这一点。进行伤口愈合和细胞计数 kit-8 实验来分析 THBS1 和 miR-338-3p 如何影响神经胶质瘤细胞的迁移和增殖能力。还分析了 miR-338-3p 对小鼠致瘤性的影响。在神经胶质瘤中观察到 miR-338-3p 下调，而 THBS1 显示相反的趋势。通过抑制 PI3K/Akt 信号通路激活，miR-338-3p 过度调节神经胶质瘤细胞在体外迁移和增殖的能力。此外，miR-338-3p 抑制体内神经胶质瘤的发展。此外，miR-338-3p直接靶向THBS1。THBS1 过表达通过增加 PI3K/Akt 磷酸化促进神经胶质瘤细胞迁移和增殖。尽管如此，miR-338-3p 过度调节减轻了 THBS1 过度表达的影响。miR-338-3p/PI3K/Akt/THBS1调控轴可以调节胶质瘤细胞增殖和迁移的进展；因此，它可以被认为是一种治疗生物标志物。