BACKGROUND Glioma has a poor prognosis, and is the most common primary and lethal primary malignant tumor in the central nervous system. Retinoic acid receptor-related orphan receptor A (RORA) is a member of the ROR subfamily of orphan receptors and plays an anti-tumor role in several cancers. METHODS A cell viability assay, the Edu assay, neurosphere formation assay, and xenograft experiments were used to detect the proliferative abilities of glioma cell line, glioma stem cells (GSCs). Western blotting, ELISAs, and luciferase reporter assays were used to detect the presence of possible microRNAs. FINDINGS Our study found for the first time that RORA was expressed at low levels in gliomas, and was associated with a good prognosis. RORA overexpression inhibited the proliferation and tumorigenesis of glioma cell lines and GSCs via inhibiting the TNF-α mediated NF-κB signaling pathway. In addition, microRNA-18a had a promoting effect on gliomas, and was the possible reason for low RORA expression in gliomas. INTERPRETATION RORA may be a promising therapeutic target in the treatment of gliomas.

中文翻译：

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使用TNF-α介导的NF-κB信号通路，MiR-18a下调的RORA抑制神经胶质瘤的增殖和肿瘤发生。

背景技术脑胶质瘤预后较差，是中枢神经系统中最常见的原发性和致死性原发性恶性肿瘤。维甲酸受体相关的孤儿受体A（RORA）是孤儿受体ROR亚家族的成员，并且在几种癌症中均具有抗肿瘤作用。方法采用细胞活力测定，Edu测定，神经球形成测定和异种移植实验检测神经胶质瘤细胞系，神经胶质瘤干细胞（GSCs）的增殖能力。蛋白质印迹，ELISA和荧光素酶报告基因检测用于检测可能的microRNA的存在。结果我们的研究首次发现RORA在神经胶质瘤中低水平表达，并且预后良好。RORA的过表达通过抑制TNF-α介导的NF-κB信号通路来抑制神经胶质瘤细胞系和GSC的增殖和肿瘤发生。另外，microRNA-18a对神经胶质瘤具有促进作用，并且可能是胶质瘤中RORA表达低的可能原因。解释RORA在神经胶质瘤的治疗中可能是有希望的治疗靶标。