Alcohol-induced C/EBP β-driven KIAA1429 decreases oxidative stress and promotes pancreatic cancer growth and metastasis via the m6A/YTHDF2/SLC43A2 pathway

Abstract

N6-methyladenosine (m6A) is implicated in tumorigenesis. To data, the role of KIAA1429, an RNA methyltransferase in pancreatic cancer (PC) has not been clearly defined. The present study demonstrated that KIAA1429 was upregulated in PC. Overexpression of KIAA1429 accelerated PC proliferation and metastasis, whereas knockdown of KIAA1429 had an opposite effect. Mechanistically, KIAA1429 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 PC. In addition, alcohol induced the expression of C/EBP β, which bound to the promoter of KIAA1429 and boosted its transcription. The findings of the present study revealed a potential link between alcohol consumption, m6A and phenylalanine absorption in PC progression, providing a novel means to combat this disease.