miR-18a 下调 RORA 通过 TNF-α 介导的 NF-κB 信号通路抑制胶质瘤的增殖和致瘤性。
MiR-18a-downregulated RORA inhibits the proliferation and tumorigenesis of glioma using the TNF-α-mediated NF-κB signaling pathway.
机构信息
Department of Neurosurgery, the First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang 110001, Liaoning, China; Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China.
Department of Neurosurgery, the First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang 110001, Liaoning, China.
出版信息
EBioMedicine. 2020 Feb;52:102651. doi: 10.1016/j.ebiom.2020.102651. Epub 2020 Feb 12.
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.
背景
神经胶质瘤预后不良，是中枢神经系统最常见的原发性致命性恶性肿瘤。维甲酸受体相关孤儿受体 A（RORA）是孤儿受体 ROR 亚家族的成员，在几种癌症中发挥抗肿瘤作用。
方法
采用细胞活力测定、Edu 检测、神经球形成检测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。采用 Western blot、ELISA 和荧光素酶报告基因检测来检测可能存在的 microRNA。
结果
我们的研究首次发现 RORA 在神经胶质瘤中低表达，并与良好的预后相关。RORA 过表达通过抑制 TNF-α 介导的 NF-κB 信号通路抑制神经胶质瘤细胞系和 GSCs 的增殖和致瘤性。此外，microRNA-18a 对神经胶质瘤具有促进作用，这可能是神经胶质瘤中 RORA 低表达的原因。
结论
RORA 可能是治疗神经胶质瘤的有前途的治疗靶点。
Zotero 插件