MiR-18a-downregulated RORA inhibits the proliferation and tumorigenesis of glioma using the TNF-α-mediated NF-κB signaling pathway
Yang Jiang,
Jinpeng Zhou,
Junshuang Zhao,
Dianqi Hou,
Haiying Zhang,
Long Li,
Dan Zou,
Jiangfeng Hu,
Ye Zhang,
Zhitao Jing
Affiliations
Yang Jiang
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
Jinpeng Zhou
Department of Neurosurgery, the First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang 110001, Liaoning, China
Junshuang Zhao
Department of Neurosurgery, the First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang 110001, Liaoning, China
Dianqi Hou
Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China
Haiying Zhang
International Education College, Liaoning University of Traditional Chinese Medicine, Shenyang, No. 79 Chongshan East Road, Shenyang 110042, Liaoning, China
Long Li
Department of Neurosurgery, the First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang 110001, Liaoning, China
Dan Zou
The First Laboratory of Cancer Institute, the First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang 110001, Liaoning, China
Jiangfeng Hu
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China
Ye Zhang
The First Laboratory of Cancer Institute, the First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang 110001, Liaoning, China
Zhitao Jing
Department of Neurosurgery, the First Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang 110001, Liaoning, China; Corresponding author.
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. Keywords: Glioma, Glioma stem cells, RORA, Tumorigenesis, microRNA-18a
