MiR-18a Downregulated RORA Inhibits the Proliferation and Tumorigenesis of Glioma Through TNF-α-Mediated NF-κB Signaling Pathway

Background: Glioma is the most common primary and lethal primary malignant tumor in central nervous system with poor prognosis. Retinoic acid receptor-related orphan receptor A (RORA) is a member of ROR subfamily of orphan receptors and plays anti-tumor role in several cancers. Methods: Cell viability assay, Edu assay, neurosphere formation assay and xenograft experiments were used to detect the proliferative ability of glioma cell lines and GSCs. Western blot, ELISA and luciferase reporter assays were used to detect the possible microRNAs. Findings: Our study found the first time RORA was lower expressed in glioma and associated with good prognosis. RORA overexpression can inhibit the proliferation and tumorigenesis of glioma cell lines and glioma stem cells (GSCs) via inhibiting TNF-αmediated NF-κB signaling pathway. Besides, miR-18a plays a promoting effect in glioma was the possible reason for lower RORA expression in glioma. Interpretation: RORA might be a promising therapeutic target in glioma treatment. Funding Statement: This work was supported by National Natural Science Foundation of China (No. 81101917, 81270036, 30901736), the Plan to Focus on Research and Development from Science and Technology project of Liaoning Province (No. 2017225029), Natural Science Foundation of Liaoning Province (No. 20170541022), Liaoning BaiQianWan Talents Program (2019-B45), Science and Technology Plan Project of Shenyang City (No. 18-014-4-11), and Fund for Scientific Research of The First Hospital of China Medical University (No. FHCMU-FSR), and Shanghai Sailing Program (No. 19YF1439000). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: This study was approved by the ethics committee of the First Affiliated Hospital of China Medical University and written informed consent was obtained from every patient. Xenografts experiment was performed in accordance with the Animal Care Committee of China Medical University.