1. Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China.
2. Department of Neurosurgery, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, Liaoning Province, P.R. China
3. Department of Neurosurgery, People's Hospital of Rugao, Jiangsu, China.
#These authors contributed equally
Glioma is a common type of tumor in the central nervous system, and the mortality is high. The prognosis of advanced glioma patients remains poor, and the therapeutic strategies need to be developed. The roles of circRNAs in glioma remain largely unknown. The aim of this study was to explore the functions circRNA_103239 in the biological behaviour changes of glioma cells. The expression of circRNA_103239 in clinical samples and glioma cells were examined using RT-qPCR. The targets of circRNA_103239 were predicted using bioinformatics approach. Gain- and loss-of-function study were carried out. The proliferation of transfected cells were evaluated by CCK-8 assay. Migratory and invasive activities of the cells were examined using wound healing, colony formation and transwell assay. Tumor growth was also evaluated in vivo. The results indicated that the expression of circRNA_103239 was predominantly detected in the cytoplasma of glioma cells. In addition, the expression of circRNA_103239 was down-regulated in glioma, and up-regulated circRNA_103239 inhibited the progression of glioma. Furthermore, miR-182-5p was the novel target of circRNA_103239 in glioma, and MTSS1 was the putative downstream molecule of circRNA_103239/miR-182-5p axis. Additionally, circRNA_103239 suppressed the progression of glioma in a miR-182-5p/MTSS1 dependent manner. Moreover, circRNA_103239 inhibited tumour growth in vivo, and the expression of circRNA_103239 was regulated by METTL14-mediated m6A modification. In summary, in normal cells, METTL14 mediated the m6A modification and expression of circRNA_103239, which sponging miR-182-5p and inducing the expression of MTSS1, subsequently inhibiting the EMT; whereas in glioma cells, downregulated METTL14 induced downregulated m6A modification and expression of circRNA_103239, further resulting in the up-regulation of miR-182-5p and down-regulation of MTSS1, consequently promoting the EMT of glioma cells and triggering the progression of tumor.
Keywords: M6A modification, circRNA_103239, glioma, miR-182-5p, MTSS1