Abnormal expression of mRNA, microRNA alteration and aberrant DNA methylation patterns in rectal adenocarcinoma

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. The miRNA, mRNA expression profiling and corresponding...

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Veröffentlicht in:PloS one 2017-03, Vol.12 (3), p.e0174461-e0174461
Hauptverfasser: Hua, Yang, Ma, Xiukun, Liu, Xianglong, Yuan, Xiangfei, Qin, Hai, Zhang, Xipeng
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Ma, Xiukun
Liu, Xianglong
Yuan, Xiangfei
Qin, Hai
Zhang, Xipeng
description 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. 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. 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. 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.
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Our study aimed to explore the potential pathogenesis of READ through integrated analysis of gene expression profiling and DNA methylation data. 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. 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. 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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. 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28350845</pmid><doi>10.1371/journal.pone.0174461</doi><tpages>e0174461</tpages><oa>free_for_read</oa></addata></record>
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subjects Adenocarcinoma - genetics
Algorithms
Analysis
Biology and life sciences
Biomarkers
Biomarkers, Tumor - genetics
Care and treatment
Cell growth
Circadian rhythms
Colorectal cancer
Colorectal surgery
Correlation
Correlation analysis
CpG Islands - genetics
Databases, Genetic
Deoxyribonucleic acid
Diagnosis
DNA
DNA Methylation
Endocrinology
Entrainment
Gastric cancer
Gene expression
Gene Expression Profiling - methods
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Health aspects
Humans
Identification
Liver cancer
Medical prognosis
Medicine and Health Sciences
Metastasis
Methylation
MicroRNA
MicroRNAs - genetics
Morbidity
Mutation
Rectal Neoplasms - genetics
Research and Analysis Methods
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
RNA
RNA, Messenger - genetics
Signal Transduction - genetics
Stomach cancer
Synapses
title Abnormal expression of mRNA, microRNA alteration and aberrant DNA methylation patterns in rectal adenocarcinoma
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