ASH1L regulates gene expression in lung cancer

ASH1L is frequently amplified and mutated in various human cancers, including lung adenocarcinoma, liver, uterine and balder cancers. We used two shRNAs to knockdown endogenous ASH1L proteins in A549 cells, and carried out RNA-seq analysis to identified the genes regulated by ASH1L. We found that compared with the control cells, 541 genes were upregulated in both ASH1L knockdown cells, whereas 398 genes were upregulated. Ingenuity Pathway Analysis (IPA) revealed that the downregulated genes are enriched in fundamental cellular activities, including cell cycle, replication, cell death and survival, and cell growth, and are important for caner and some other diseases . Gene Ontology (GO) analysis also revealed similar cellular pathways that the downregulated genes are involved, whereas the upregulated genes are not enriched in any specific pathways that are statistically significant. Taken together, these data suggest that ASH1L has an oncogenic role in lung adenocarcinoma promoting cancer cell growth, therefore may serve as a potential therapeutic target for the treatment of lung adenocarcinoma patients that have ASH1L amplifications. Overall design: A549 cells were transduced with two shRNAs targeting ASH1L and one control non-targeting shRNA and selected with puromycin for 4-6 days. RNA-seq was then performed to identify differentially expressed genes among different conditions.