LncRNA FAM83H-AS1 inhibits ferroptosis of endometrial cancer by promoting DNMT1-mediated CDO1 promoter hypermethylation.

Endometrial cancer (EC) is the most prevalent gynecological epithelial malignancy. DNA methylation is a promising cancer biomarker but limited use for detecting EC. We previously found that the level of cysteine dioxygenase 1 (CDO1) promoter methylation was elevated in EC patients through methylomics, but the role and mechanism of CDO1 in EC remained unclear. Here, the methylation level of CDO1 promoter was detected by bisulfite-sequencing PCR and methylation-specific PCR (bisulfite conversion-based PCR methods, which remain the most commonly used techniques for methylation detection). Cells were incubated with erastin (the ferroptosis activator). Cell vitality was measured using the cell counting kit-8 assay. FAM83H-AS1 cellular distribution was analyzed by the fluorescence in situ hybridization assay. Lipid reactive oxygen species level was examined by BODIPY-C11 staining. The interactions between FAM83H-AS1, CDO1, and DNA methyltransferase1 (DNMT1) were analyzed by RNA-binding protein immunoprecipitation or chromatin immunoprecipitation assay. The xenograft mouse model was utilized to test CDO1 and FAM83H-AS1's influence on tumor development in vivo. Results showed that CDO1 was hypermethylated and downregulated in EC. CDO1 knockdown reduced erastin-induced ferroptosis in EC cells. Mechanistically, DNMT1 is a DNA methyltransferase, which can transfer methyl groups to cytosine nucleotides in genomic DNA. Long noncoding RNA FAM83H-AS1 increased CDO1 promoter methylation level and inhibited its expression in EC cells by recruiting DNMT1. CDO1 knockdown or FAM83H-AS1 overexpression promoted EC tumor growth in vivo. Long noncoding RNA FAM83H-AS1 inhibited ferroptosis in EC by recruiting DNMT1 to increase CDO1 promoter methylation level and inhibit its expression.