LncRNA DNM3OS Promotes Tumorigenesis of Liver Cancer by Inducing FOXO3a Methylation via Interacting with DNMT1

Background and Objective: DNM3OS (Dynamin 3 Opposite Strand/Antisense RNA) is a hepatocellular carcinoma (HCC)-related long noncoding RNA. We aim to investigate whether DNM3OS regulates the growth of HCC cells by the DNA methyl-transferase 1 (DNMT1)/Forkhead box O3a (FOXO3a) pathway.Methods: LncRNAs related to liver cancer were identified by searching the LncRNADisease v2.0 database. DNM3OS and FOXO3a expression levels were detected through qRT-PCR in clinical specimens, as well as in THLE-2, SK-HeP1, and Huh-7 cells. CHIP (Chromatin Immunoprecipitation) and RIP (RNA immunoprecipitation) assays were used to detect the interaction of DNM3OS and methyltransferase. A tumor formation experiment was used to detect growth of HCC cells into a tumor in nude mice.Results: In liver cancer patients, DNM3OS was highly expressed whilst the expression of FOXO3a was low. DNM3OS promoted the methylation in the FOXO3a promoter region and inhibited the transcription of FOXO3a.Conclusions: The lncRNA DNM3OS works as an oncogene that encourages liver cancer progression by promoting methylation of the FOXO3a promoter via DNMT1. Our research provides new clues for clarifying the molecular mechanisms underlying HCC.