Alcohol-induced C/EBP ß-driven VIRMA decreases oxidative stress and promotes pancreatic ductal adenocarcinoma growth and metastasis via the m6A/YTHDF2/SLC43A2 pathway

N6-methyladenosine (m6A) is implicated in tumorigenesis. To data, the role of VIRMA, an RNA methyltransferase in pancreatic ductal adenocarcinoma (PDAC) has not been clearly defined. The present study demonstrated that VIRMA was upregulated in PDAC. Overexpression of VIRMA accelerated PDAC proliferation and metastasis, whereas knockdown of VIRMA had an opposite effect. Mechanistically, VIRMA promoted the degradation of SLC43A2 mRNA via an m6A-YTHDF2 mechanism, and downregulation of SLC43A2 reduced phenylalanine absorption and oxidative stress, thus enhancing the progression of PDAC. In addition, alcohol induced the expression of C/EBP ß, which bound to the promoter of VIRMA and boosted its transcription. The findings of the present study revealed a potential link between alcohol consumption, m6A and phenylalanine absorption in PDAC progression, providing a novel means to combat this disease. Overall design: To reveal the m6A modified genes in pancreatic cancer cells, m6A-seq and mRNA-seq performed by deep sequencing, using Illumina HiSeq 4000.