title: Abnormal expression of mRNA, microRNA alteration and aberrant DNA methylation patterns in rectal adenocarcinoma.
abstract: OBJECTIVE
  Rectal adenocarcinoma (READ) is a malignancy cancer with the high morbidity and motility worldwide. Our study aimed to explore the potential pathogenesis of READ through integrated analysis of gene expression profiling and DNA methylation data.
  
  
  METHODS
  The miRNA, mRNA expression profiling and corresponding DNA methylation data were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs/ miRNAs/methylated regions (DEmRNA/DEmiRNAs) were identified in READ. The negatively correlation of DEmiRNA-DEmRNAs and DNA methylation-DEmRNAs were obtained. DEmRNAs expression was validated through quantitative real-time polymerase chain reaction (qRT-PCR) and microarray expression profiling analyses.
  
  
  RESULTS
  1192 dysregulated DEmRNAs, 27 dysregulated DEmiRNAs and 6403 aberrant methylation CpG sites were screened in READ compared to normal controls. 1987 negative interaction pairs among 27 DEmiRNAs and 668 DEmRNAs were predicted. 446 genes with aberrant methylation were annotated. Eventually, 50 DEmRNAs (39 down- and 11 up-regulated DEmRNAs) with hypermethylation, synchronously negatively targeted by DEmiRNAs, were identified through the correlation analysis among 446 genes with aberrant methylation and 668 DEmRNAs. 50 DEmRNAs were significantly enriched in cAMP signaling pathway, circadian entrainment and glutamatergic synapse. The validation results of expression levels of DEmRNAs through qRT-PCR and microarray analyses were compatible with our study.
  
  
  CONCLUSIONS
  7 genes of SORCS1, PDZRN4, LONRF2, CNGA3, HAND2, RSPO2 and GNAO1 with hypermethylation and negatively regulation by DEmiRNAs might contribute to the tumorigenesis of READ. Our work might provide valuable foundation for the READ in mechanism elucidation, early diagnosis and therapeutic target identification.
authors.affiliation: Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Department of Surgery, Sino-Singapore Eco-City Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Xiukun
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tianjin Institute of Integrative Medicine for Acute Abdominal Diseases, Nankai Hospital, Tianjin, China.
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.
authors.forename: Xipeng
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012004:Rectal Neoplasms / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger