In vivo CRISPR screening unveils histone demethylase UTX as an important epigenetic regulator in lung tumorigenesis

Abstract

Significance Tumor suppressor genes (TSGs) play important roles in lung cancer initiation, progression, and even metastasis. Here, we take advantage of the clustered regularly interspaced short palindromic repeats/Cas9-mediated screening in vivo technique to identify multiple tumor suppressor genes contributing to lung cancer malignant progression. Using genetically engineered mouse models, we further confirm the tumor-suppressive role of epigenetic regulator UTX and provide therapeutic implications for UTX-deficient lung tumors. Thus, our work provides a systematic screening of TSGs in vivo and demonstrates UTX functions as the important epigenetic regulator in lung tumorigenesis.