ARID1A Loss Promotes Lung Adenocarcinoma by Remodeling Chromatin Accessibility and Activating Glycolytic Reprogramming

This study demonstrated that ARID1A loss markedly promotes lung tumorigenesis in genetic mice models. RNA sequencing reveals significant enrichment of the glycolytic pathway in ARID1A-deficient tumors, which is characterized by the upregulation of PGAM1, PKM2, and PGK1. Besides, ARID1A depletion increases chromatin accessibility and enhances the binding ability of Hif-1a to the promoter regions of Pgam1, Pkm, and Pgk1. In patients with lung cancer, ARID1A status is negatively correlated with mRNA level of PGAM1, PKM, and PGK1. Overall design: RNA-Seq; ATAC-seq and ChIP-seq