TAL1-mediated epigenetic modifications down-regulate the expression of GIMAP family in non-small cell lung cancer

Abstract

AbstractBackgroudThe study was designed to explore the role of GIMAP family in non-small cell lung cancer (NSCLC) and its possible expression regulation mechanisms using existing biological databases including encyclopedia of DNA elements (ENCODE), gene expression omnibus (GEO), and the cancer genome atlas (TCGA).MethodsLung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) were used to evaluate the expression of GIMAPs in TCGA. Five NSCLC datasets were then selected from GEO for validation. RNA-seq and Chip-seq data from ENCODE and GEO were used to observe epigenetic modifications on the chromosomes of GIAMPs in NSCLC. We constructed protein-protein interaction (PPI) network to reveal the main interacting proteins of GIMAPs. We then analyzed the correlation and regulatory mechanism between TAL1 and the expression of GIMAP family. We also used Kaplan-Meier for survival analysis.ResultsAll 7 genes in the GIMAP family were down-regulated in NSCLC. H3K4me3 and H3K27ac disappeared, while H3K27me3 increased on the chromosome of this family. The expression of TAL1 was positively correlated with the expression of GIMAPs. sh-TAL1 significantly down-regulated the expression of GIMAP family through epigenetic modification. High expression of GIMAPs and TAL1 was found to be associated with a good prognosis of NLCSC.ConclusionThe downregulation of TAL1 caused the disappearance of H3K27ac and H3K4me3. It also caused an increase in H3K27me3 on the GIMAPs gene, eventually leading to the overall downregulation of the GIMAP family genes.