Abstract
Objective miRNA has gained attention as a therapeutic target in various malignancies. The proposal of this study was to investigate the biological functions of key miRNAs and target genes in cancers of the digestive tract which include esophageal carcinoma (ESCA), gastric adenocarcinoma (GAC), colon adenocarcinoma (COAD), and rectal adenocarcinoma (READ). Materials and Methods After screening differentially expressed miRNAs (DEMIs) and differentially expressed mRNAs (DEMs) in four digestive cancers from The Cancer Genome Atlas (TCGA) database, the diagnostic value of above DEMIs was evaluated by receiver-operating characteristic (ROC) curve analysis. Then, corresponding DEMIs' target genes were predicted by miRWalk 2.0. Intersection of predicted target genes and DEMs was taken as the target genes of DEMIs, and miRNA-mRNA regulatory networks between DEMIs and target genes were constructed. Meanwhile, the univariate Cox risk regression model was used to screen miRNAs with distinct prognostic value, and Kaplan–Meier analysis was used to determine their significance of prognosis. Furthermore, we performed bioinformatics methods including protein-protein interaction (PPI) networks, gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene group RIDA analysis by Gene-Cloud of Biotechnology Information (GCBI) to explore the function and molecular mechanisms of DEMIs and predicted target genes in tumor development. Results Eventually, 3 DEMIs (miR-7-3, miR-328, and miR-323a) with significant prognostic value were obtained. In addition, 3 DEMIs (miR-490-3p, miR-133a-3p, and miR-552-3p) and 281 target genes were identified, and the 3 DEMIs showed high diagnostic value in READ and moderate diagnostic value in ESCA, GAC, and COAD. Also, the miRNA-mRNA regulatory network with 3 DEMIs and 281 overlapping genes was successfully established. Functional enrichment analysis showed that 281 overlapping genes were mainly related to regulation of cell proliferation, cell migration, and PI3K-Akt signaling pathway. Conclusion The diagnostic value and prognostic value of significant DEMIs in cancers of the digestive tract were identified, which may provide a novel direction for treatment and prognosis improvement of cancers of the digestive tract.
Highlights
Cancer of the digestive tract is one of the most common malignancies in the world, and it is a common high-risk malignancy in China, mainly including esophageal carcinoma (ESCA), gastric adenocarcinoma (GAC), colorectal cancer (CRC), and rectal adenocarcinoma (READ)
BioMed Research International were estimated to occur in 2018. ey were colorectal cancer (6.1%), stomach cancer (5.7%), and esophagus cancer (3.2%) with 1,096,601, 1,033,701, and 572,034 incidences, respectively [2]. e prognosis of cancers of the digestive tract is poor because of the advanced stage at the time of being diagnosed. us, early and timely diagnosis is of great importance for patients with cancers of the digestive tract which determines whether the patient can receive radical surgical treatment or not [3, 4]. erefore, reliable biomarkers are urgently required for detection of the cancers of the digestive tract in primary stages to improve the adverse outcome of patients [5]
We evaluated the prognostic value of three differentially expressed miRNAs (DEMIs) by univariate Cox risk regression model analysis. e DEMIs above were further screened by matching with survival time and removing more than 10% missing values
Summary
Cancer of the digestive tract is one of the most common malignancies in the world, and it is a common high-risk malignancy in China, mainly including esophageal carcinoma (ESCA), gastric adenocarcinoma (GAC), colorectal cancer (CRC), and rectal adenocarcinoma (READ). We aim to find potential biomarkers for early diagnosis and explore their molecular mechanisms in cancers of the digestive tract. MicroRNA (miRNA) is an endogenous noncoding RNA with a length of about 22 nucleotides [6] It plays an oncogene or tumor suppressor role in biological function by regulating target genes, which can inhibit the translation of protein via binding directly to specific sequences of target gene transcription through regulatory mechanisms including positive regulation of mRNA targets and induction of direct degradation of mRNA [7]. Erefore, the purpose of our study was to find the diagnostic and prognostic value of key miRNAs, and the biological function of target genes in cancers of the digestive tract needs to be better elucidated More and more evidence has demonstrated that many key miRNAs participated in the initiation and progression of cancers of the digestive tract [9,10,11]. erefore, the purpose of our study was to find the diagnostic and prognostic value of key miRNAs, and the biological function of target genes in cancers of the digestive tract needs to be better elucidated
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