MUC1-C auto-regulatory complex with EBNA1 is responsible for latent Epstein-Barr virus-associated gastric cancer progression.

ABSTRACT: Latent Epstein-Barr Virus (EBV) infection promotes cancers derived from B-lymphocytes and epithelial cells by mechanisms that largely remain unclear. EBV-encoded nuclear antigen 1 (EBNA1) is uniformly expressed in EBV-associated cancers; however, how EBNA1 contributes to cancer progression is not known. The MUC1 gene evolved in mammals to protect barrier tissues from viral infections. We report that MUC1 is upregulated in EBV-associated gastric cancers (EBVaGCs). Our results demonstrate that EBNA1 and the oncogenic MUC1-C subunit form an auto-regulatory complex that controls expression of EBNA1, MUC1-C and host cellular genes. EBNA1 appropriates MUC1-C to (i) induce DNA methyltransferase (DNMT) expression and DNA methylation, (ii) suppress CDKN1A encoding p21 to promote proliferation, and

SUBMITTER: Ozawa H 

PROVIDER: S-EPMC12436189 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature