Glioma is one of the most common malignant tumors and shows a high metastasis rate and poor prognosis. Abnormal expression of long non-coding RNAs (lncRNAs) contributes to various human tumors including gliomas. This study aimed to investigate the regulatory role of the antisense RNA of growth arrest special 5 (GAS5-AS1), a novel lncRNA, in gliomas. Expression of GAS5-AS1 and microRNA-106b-5p (miR-106b-5p) in glioma tissues and cells was detected by quantitative reverse transcription PCR, northern blotting, or fluorescent in situ hybridization. Cell proliferation, migration, and invasion were analyzed by CCK-8 and Transwell assays. BALB/c nude mice were used to establish a glioma xenograft animal model by subcutaneous injection of U251 cells transfected with small interfering RNA targeting GAS5-AS1. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between GAS5-AS1 and miR-106b-5p. GAS5-AS1 expression was downregulated in glioma tissues and cells, and upregulation of GAS5-AS1 expression inhibited glioma cell proliferation, migration, and invasion. GAS5-AS1 expression was correlated with the glioma tumor grade. In nude mice, upregulation of GAS5-AS1 markedly suppressed glioma tumor growth. GAS5-AS1 overexpression significantly increased the miR-106b-5p level in glioma cells, and GAS5-AS1 expression was negatively related to miR-106b-5p expression in glioma tissues. Overexpression of miR-106b-5p reversed the inhibitory effects of GAS5-AS1 upregulation on glioma cell proliferation and metastasis, while restoration of TUSC2 rescued the proliferation and invasion of glioma cells transfected with miR-106b-5p mimics. In summary, lncRNA GAS5-AS1 inhibited glioma proliferation, migration, and invasion by sponging miR-106b-5p and regulating the expression of TUSC2. Our results suggest GAS5-AS1 as a novel target for the treatment and prognosis prediction of gliomas.

中文翻译：

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LncRNA GAS5-AS1 通过 miR-106b-5p/TUSC2 轴抑制神经胶质瘤的增殖、迁移和侵袭。

胶质瘤是最常见的恶性肿瘤之一，转移率高，预后差。长链非编码 RNA (lncRNA) 的异常表达会导致包括神经胶质瘤在内的各种人类肿瘤。本研究旨在研究一种新型 lncRNA 的反义 RNA 生长停滞特殊 5 (GAS5-AS1) 在胶质瘤中的调节作用。通过定量逆转录PCR、northern印迹或荧光原位杂交检测胶质瘤组织和细胞中GAS5-AS1和microRNA-106b-5p (miR-106b-5p)的表达。通过 CCK-8 和 Transwell 测定分析细胞增殖、迁移和侵袭。使用BALB/c裸鼠皮下注射转染靶向GAS5-AS1的小干扰RNA的U251细胞建立胶质瘤异种移植动物模型。进行双荧光素酶报告基因测定以确认 GAS5-AS1 和 miR-106b-5p 之间的靶向关系。胶质瘤组织和细胞中 GAS5-AS1 表达下调，而 GAS5-AS1 表达上调抑制胶质瘤细胞增殖、迁移和侵袭。GAS5-AS1 表达与胶质瘤肿瘤分级相关。在裸鼠中，GAS5-AS1 的上调显着抑制了胶质瘤的生长。GAS5-AS1过表达显着增加了胶质瘤细胞中miR-106b-5p的水平，并且GAS5-AS1的表达与胶质瘤组织中的miR-106b-5p表达呈负相关。miR-106b-5p的过表达逆转了GAS5-AS1上调对胶质瘤细胞增殖和转移的抑制作用，而 TUSC2 的恢复挽救了转染 miR-106b-5p 模拟物的胶质瘤细胞的增殖和侵袭。总之，lncRNA GAS5-AS1 通过海绵化 miR-106b-5p 和调节 TUSC2 的表达来抑制胶质瘤的增殖、迁移和侵袭。我们的研究结果表明 GAS5-AS1 作为胶质瘤治疗和预后预测的新靶点。