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

Abstract

AimRectal 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.MethodsThe 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.Results1192 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.Conclusion7 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.

MicroRNA‐29b regulatesDNAmethylation by targeting Dnmt3a/3b and Tet1/2/3 in porcine early embryo development

“…DNA methylation is crucial for mammalian embryo development which is dynamically regulated by the action of the DNA methyltransferases (DNMTs) and ten eleven translocation enzymes (TETs) (Ambrosi, Manzo, & Baubec, ; Li & Zhang, ; Lim, Knowles, Solter, & Messerschmidt, ). As both targets and effectors of DNMTs and TETs, miRNAs play pivotal roles in regulating DNA methylation (Hua et al., ; Jin, Li, Ouyang, Tan, & Jiang, ; Shivakumar et al., ). DNA methylation can inhibit the transcription of miRNAs by methylating the CpG islands in the promoter regions of miRNAs, and certain miRNAs can directly target DNA methylation‐related enzymes, thereby affecting the whole genome methylation pattern (Chhabra, ).…”

Comprehensive analysis identifying aberrant DNA methylation in rectal mucosa from ulcerative colitis patients with neoplasia

“…HAND2 is a basic helix-loop-helix transcription factor that plays a very important role in the development and differentiation of the heart and nervous system [ 26 ]. Recent studies revealed that HAND2 was significantly hypermethylated and downregulated in colon and rectal cancer [ 27 , 28 ]. In addition, continuous proliferation of the endometrium was observed in mice with knockdown of HAND2 [ 29 ].…”

MicroRNA: Another Pharmacological Avenue for Colorectal Cancer?

“…Studies have suggested that other mechanisms are also involved in colorectal cancer. Hua et al (2017) used TCGA database to explore mRNA expression profiling and corresponding DNA methylation data. Eventually, 50 differentially expressed (DE) mRNAs DEmRNAs (39 down- and 11 upregulated DEmRNAs) with hypermethylation, synchronously negatively targeted by DEmiR, were identified through the correlation analysis among 446 genes with aberrant methylation and 668 miR, evidenced from rectal adenocarcinoma tumor samples.…”

“…Eventually, 50 differentially expressed (DE) mRNAs DEmRNAs (39 down- and 11 upregulated DEmRNAs) with hypermethylation, synchronously negatively targeted by DEmiR, were identified through the correlation analysis among 446 genes with aberrant methylation and 668 miR, evidenced from rectal adenocarcinoma tumor samples. They further used qRT-PCR and microarray analyses to validate and identified 7 genes of SORCS1, PDZRN4, LONRF2, CNGA3, HAND2, RSPO2, and GNAO1 with hypermethylation and negatively regulation by DEmiR, the seven of which might contribute to the tumorigenesis of rectal adenocarcinoma ( Hua et al, 2017 ). Stable expression of SNAI1 in DLD1 and HCT116 cells downregulates miR-145 expression compared to control cells.…”