Screening critical genes for rectal adenocarcinoma using combined mRNA,microRNA alteration and aberrant DNA methylation patterns / 天津医药

ABSTRACT

Objective To study the underlying pathogenesis of rectal adenocarcinoma (READ) by analyzing the expression data of high throughput miRNA/mRNA and DNA methylation. Methods The miRNA/ mRNA expression profiling and corresponding DNA methylation data were downloaded from the Cancer Genome Atlas(TCGA)database.The differentially expressed mRNAs (DEmRNA)/miRNAs (DEmiRNAs)/methylated regions were identified in READ. The negatively correlation of DEmiRNA-DEmRNAs and DNA methylation-DEmRNAs were obtained.DEmRNA expression was validated through quantitative real-time polymerase chain reaction (qRT-PCR) analyses. Results A total of 1 192 DEmRNAs and 27 DEmiRNAs were screened in the data.And 1 987 miRNA-mRNA regulatory relationships were obtained by screening target genes.In this study,446 genes with aberrant methylation were annotated,and 6 403 aberrant methylation CpG sites were screened in READ compared to normal controls.Eventually,50 DEmRNAs(39 down-regulated and 11 up-regulated DEmRNAs)with hyper methylation and synchronously negatively targeted by DEmiRNAs,were identified through the correlation analysis among 446 genes with aberrant methylation and 668 DEmRNAs. The 50 DEmRNAs were significantly enriched in cAMP signaling pathway, circadian entrainment and glutamatergic synapse. Results of qRT-PCR showed that the validation results of expression levels of DEmRNAs were compatible with our study. Conclusion Seven hypermethylation genes(SORCS1,PDZRN4,LONRF2,CNGA3,HAND2,RSPO2 and GNAO1)that are negatively regulated by DEmiRNAs may promote the occurrence of READ.