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<p>N6-methyladenosine (m6A) plays a role in the development of tumors. However, the specific role of VIRMA, an RNA methyltransferase, in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study shows that VIRMA expression is elevated in PDAC. Increased VIRMA levels promoted PDAC growth and spread, while reducing VIRMA expression slowed these processes. VIRMA facilitated SLC43A2 mRNA degradation through an m6A-YTHDF2 pathway. The resulting decrease in SLC43A2 reduced phenylalanine absorption and oxidative stress, further driving PDAC progression. Furthermore, alcohol increased C/EBP β expression, which bound to VIRMA’s promoter, enhancing its transcription. These findings suggest a connection between alcohol consumption, m6A modifications, and phenylalanine absorption in PDAC progression, offering a new approach to combat this disease.</p>

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

  • 期刊论文

  • 发表日期：

    2025年2月3日

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  • Lei Gao,
  • Gaoyuan Lv,
  • Ziying Liu,
  • Yitong Tian,
  • Fang Han,
  • Le Li,
  • Gang Wang,
  • Yuhua Zhang

摘要

N6-methyladenosine (m6A) plays a role in the development of tumors. However, the specific role of VIRMA, an RNA methyltransferase, in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study shows that VIRMA expression is elevated in PDAC. Increased VIRMA levels promoted PDAC growth and spread, while reducing VIRMA expression slowed these processes. VIRMA facilitated SLC43A2 mRNA degradation through an m6A-YTHDF2 pathway. The resulting decrease in SLC43A2 reduced phenylalanine absorption and oxidative stress, further driving PDAC progression. Furthermore, alcohol increased C/EBP β expression, which bound to VIRMA’s promoter, enhancing its transcription. These findings suggest a connection between alcohol consumption, m6A modifications, and phenylalanine absorption in PDAC progression, offering a new approach to combat this disease.