RETRACTED: DNA Methyltransferase Inhibitor 5-AZA-DC Regulates TGFβ1-Mediated Alteration of Neuroglial Cell Functions after Oxidative Stress (Retracted Article)

摘要

5-AZA-DC is an efficient methylation inhibitor that inhibits methylation of target DNA. In this study, we explored the effects of 5-AZA-DC on the regulation of TGF beta 1 on target genes in neuroglial cell, as well as neuroglial cell functions under oxidative stress. The oxidative stress was constructed by editing CRISPR/Cas9 for knock out Ang-1 and ApoE4 genes. Cells were subjected to TGF beta 1(OE) (or shTGF beta 1) transfection and/or 5-AZA-DC intervention. Results showed that under oxidative stress, both TGF beta 1(OE) and shTGF beta 1 transfection raised DNMT1, but reduced TGF beta 1, PTEN, and TSC2 expressions in neuroglial cells. TGF beta 1 directly bind to the promoter of PTEN gene. 5-AZA-DC intervention lowered DNMT1 and raised TGF beta 1 expression, as well as promoted the binding between TGF beta 1 and promoter of PTEN. TGF beta 1(OE) caused a significant increase in the DNA demethylation level of PTEN promoter, while 5-AZA-DC intervention reduced the DNA demethylation level of PTEN promoter. Under oxidative stress, TGF beta 1(OE) (or shTGF beta 1) transfection inhibited neuroglial cell proliferation, migration, and invasion, promoted cell apoptosis. 5-AZA-DC intervention alleviated TGF beta 1(OE) (or shTGF beta 1) transfection caused neuroglial cell proliferation, migration, and invasion inhibition, as well as cell apoptosis. To conclude, these results suggest that 5-AZA-DC can be used as a potential drug for epigenetic therapy on oxidative stress damage in neuroglial cells. The findings of this research provide theoretical basis and research ideas for methylation drug intervention and TGF beta 1 gene as a possible precise target of glial oxidative stress diagnosis and treatment.

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