RNA N6-methyladenosine demethylase FTO targets MOXD1 promoting the malignant phenotype of gastric cancer

Abstract

BackgroundThe m6A modified demethylase FTO affects the progression of gastric cancer (GC), and the role mechanism of FTO in GC is still unclear. We, here, explored the role of FTO and unrevealed the mechanisms of its function in GC.MethodsThe expression and clinical prognosis of FTO in GC were examined via UALCAN and GEPIA online databases. Effect of FTO shRNA on GC cellular malignant phenotype were proved by CCK-8, Transwell, Wound healing assay and Flow cytometric assay. RNA-sequencing data of FTO depleted AGS cells were downloaded to analyze differentially expressed genes of FTO downstream. The GO and KEGG pathway enrichment were performed for the DEGs by DAVID. RT-qPCR and RIP-qPCR assay were applied to verify the MOXD1 mRNA and methylated mRNA in FTO shRNA group. The expression and clinical prognosis of MOXD1 in GC were explored via UALCAN, GEPIA and Kaplan-Meier plotter. The role and mechanism and of MOXD1 in GC cell lines were detected and analyzed.ResultsThe expression of FTO was found to be elevated in GC tissues compared with normal tissues, and worse survival were strongly related to high expression of FTO in GC. FTO silencing suppressed the proliferation, migration and promoted apoptosis of GC cells. A total of 5856 DEGs were obtained in between NC and FTO depleted AGS cell groups, and involved in the cancer related pathways. Here, FTO targets MOXD1 mRNA and promotes its expression via m6A methylation. MOXD1 upregulation was associated to poor prognosis of GC. MOXD1 silencing suppressed the malignant phenotype of GC cells. MOXD1 activated cancer -related signaling pathway (MAPK, TGF-β, NOTCH and JAK/STAT).ConclusionsOur study demonstrated that FTO silencing decreased MOXD1 expression to inhibit the progression of GC via m6A methylation modification. FTO/MOXD1 may be potential targets for the treatment and prognosis of GC.