METTL3 mediated m6A methylation of HIF-1 α promoted progression in glioma

Abstract

Abstract Background Glioma was a malignant tumor of the central nervous system. m6A methylation and HIF-1α were related to the occurrence and development of gliomas. However, the co-mechanism of m6A methylation and HIF-1α in glioma is unclear. Objective This aim was to determine the m6A methylation of HIF-1α in glioma. Methods Elisa and dot blot were used to detect m6A level. The changes of related genes, biological pathways and gene ontology were analyzed by bioinformatics. METTL3 and HIF-1α were knockdown by sh-RNA, and the mRNA and protein level were detected by qPCR and western blot. In addition, the m6A RNA methylation sites were predicted and verified by m6A-RIP-MMP-6 analysis༎ Results We found that compared with paracancerous, the mRNA and protein levels of m6A were dramatically increased in glioma. The biological different were found in glioma and paracancerous. Moreover, glioma had highly mRNA and protein level of HIF-1α. METTL3 and HIF- 1α knockdown can significantly decrease the growth of glioma cells. Furthermore, we confirmed the m6A RNA methylation site in HIF-1α. Finally, we found that METTL3 regulated the m6A level and RNA stability of HIF-1α. Conclusion Our finding demonstrated that the co-mechanism of m6A methylation of HIF-1α and METTL3 in glioma, and may be helpful in the treatment of glioma.