HERVH-derived eRNA activates a super-enhancer-driven ALDH1A3/SAT1 axis to promote ferroptosis escape and pancreatic cancer development.

ABSTRACT: Endogenous retroviruses (ERVs), widely distributed in the human genome, are usually epigenetically silenced but can be reactivated in cancer. Activated ERVs may act as regulatory elements or produce noncoding RNAs that modulate gene expression and affect tumor biology. Their role in pancreatic ductal adenocarcinoma (PDAC), particularly in ferroptosis regulation, remains unclear. Here, we identify human endogenous retrovirus-H (HERVH) derived enhancer RNAs (eRNAs) aberrantly overexpressed in PDAC by integrating gene expression and histone modification data. Silencing HERVH markedly suppresses PDAC proliferation and tumor growth. Mechanistically, HERVH transcription is driven by the super-enhancer-associated transcription factor Krüppel-like factor 5 (KLF5), and HERVH eRNAs cooperate with KL

SUBMITTER: Yuan L 

PROVIDER: S-EPMC12693981 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature