Oncogenic fatty acid oxidation senses sleep deficiency-induced circadian disruption to promote tumorigenesis [Ctrl vs SD]

Insufficient sleep and circadian disruption are associated with poor prognosis in cancer patients, yet how sleep deficiency (SD) disrupts circadian cellular biological process that promote tumor growth and development remains elusive. To investigate the effects of sleep deficiency on tumorigenesis, we evaluated the gene expression in the lung from KRASG12D/WT mice after sleep deficient treatment (7 weeks). Analyzing Gene Ontology (GO) Enrichment of significantly up-regulated genes from lung tumors of SD mice, we found that lipid metabolism processes were enriched in the top 20 GO terms. Lipid metabolomics results showed that SD dramatically stimulates fatty acid oxidation process during lung tumorigenesis. Moreover, genetic ablation of ACSL1, a key regulatory factor in FAO, marked reversed SD-promoted lung tumor development. In addition, SD triggered fatty acid oxidation to enhance cancer stem-like properties. Overall design: RNA-seq data of the lung tumor in Ctrl and SD group in the KrasLSL-G12D/WT lung tumor model.