METTL3 relieved the injury of SH-SY5Y cells treated with lipopolysaccharide and exposed to sevoflurane through regulating the m6A levels of Sox2.

Abstract

Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly patients. The objective of this study was to investigate the role of methyltransferase 3 (METTL3) in the POCD progression. The SH-SY5Y cells were treated with lipopolysaccharide (LPS) and exposed to sevoflurane to establish a POCD cell model. The cell viability and proliferation were assessed with MTT and EdU assays. Besides, the cell apoptosis was determined with TUNEL staining and flow cytometry. Additionally, the inflammatory factors were measured with ELISA. N6-methyladenosine (m6A) RNA Methylation Quantification Kit was used to detect the m6A levels. The relative expressions of methyltransferase 3 (METTL3) and Sex-determining region Y-box-2 (Sox2) was measured with RT-qPCR and western blot assays. RNA methylation immunoprecipitation-real-time quantitative PCR was performed to detect the RNA that was m6A modified. After LPS treatment and sevoflurane exposure, the cell viability and proliferation were decreased and the cell apoptosis was elevated. The m6A and the METTL3 expression levels in the POCD cell model were declined. METTL3 overexpression promoted the cell growth and inhibited the cell apoptosis in the POCD cell model. Besides, the Sox2 levels were reduced in the POCD cell model. METTL3 silencing declined the m6A and mRNA levels of Sox2, while overexpression of METTL3 elevated it. The relationship between METTL3 and Sox2 was confirmed with double luciferase assay. Finally, Sox2 silencing neutralized the role of METTTL3 overexpression in the POCD cell model. METTL3 relieved the injury of the SH-SY5Y cells induced by LPS treatment and sevoflurane exposure through regulating the m6A and mRNA levels of Sox2.