DNMT1-dependent DNA methylation of lncRNA FTX inhibits the ferroptosis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most malignant solid tumors worldwide. Long non-coding RNAs (lncRNAs) are the key factor in the pathogenesis of HCC. This study aimed to investigate the roles of lncRNA FTX in HCC. mRNA levels were detected using RT-qPCR. Protein expression was determined using western blot. cellular functions were determined using CCK-8 and PI staining assay. RNA fluorescent in situ hybridization (FISH) assay was conducted to analyze the location of lncRNA FTX and DNMT1. RNA pulldown, RNA immunoprecipitation (RIP), and chromatin-immunoprecipitation (ChIP) assays were used to ascertain the involved mechanisms. We found that FTX was downregulated in HCC patients, which was associated with poor prognosis. Moreover, DNMT1-mediated methylation of FTX promoter inhibited its expression. Interestingly, overexpression of FTX promoted the ferroptosis of HCC cells. FTX sponged miR-374b-3p to upregulate TFRC expression. However, downregulation of miR-374b-3p or overexpression of TFRC alleviated the effects of FTX knockdown and promoted the survival of HCC cells. In conclusion, DNMT1-dependent DNA methylation of FTX promotes the development of HCC through regulating miR-374b-3p/TFRC axis. Therefore, DNMT1/FTX/miR-374b-3p/TFRC axis may be a potential target for HCC.