N6-methyladenosine Reader YTHDF1-induced lncRNA DLGAP1-AS2 Promotes the c-Myc Mediated Gastric Cancer Aerobic Glycolysis

Abstract

Background: Emerging data has demonstrated the essential function of N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) in human tumorigenesis. Nevertheless, the regulation of m6A-lncRNA approach on gastric cancer (GC) tumorigenesis is unclear. Methods: LncRNA expression profile data was derived from GEO. M6A profile was screened using Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). The metabolism assays were conducted using quantitative analysis of glucose, lactate, ATP and extracellular acidification rate (ECAR). The m6A level of specific RNA was identified using MeRIP-qPCR. The molecular interaction was detected using RIP assay.Results: In the findings, results showed that enhanced DLGAP1-AS2 expression was correlated with advanced pathological stage and poor prognosis. Functionally, DLGAP1-AS2 promoted the aerobic glycolysis and knockdown of DLGAP1-AS2 suppressed the tumor growth of GC cells. Mechanistically, m6A reader YTHDF1 accelerated the enrichment of DLGAP1-AS2 in GC. Moreover, DLGAP1-AS2 interacted with YTHDF1 to integrate c-Myc mRNA, thereby enhancing the stability of c-Myc mRNA through DLGAP1-AS2/m6A/YTHDF1/c-Myc mRNA. Conclusions: In conclusion, our work indicates a novel m6A-maintained lncRNA DLGAP1-AS2 in the GC aerobic glycolysis, disclosing a m6A-reader-dependent modality regulation.