Construction and Comprehensive Analysis of the Competing Endogenous Rna Network in Endometrial Adenocarcinoma

Abstract

Background: Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors. In this study, we constructed gene co-expression networks to identify key modules and hub genes involved in the pathogenesis of EC. Methods: The RNA profiles of adenocarcinoma and non-adenocarcinoma tissues of patients with EC from The Cancer Genome Atlas were analyzed. MicroRNA, mRNA, and long non-coding RNA networks were constructed based on the differentially expressed RNAs between the two tissues. RNAs from the competing endogenous RNA (ceRNA) networks were then used to construct co-expression networks by weighted gene co-expression network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed by the Database for Annotation, Visualization and Integrated Discovery tool. Results: The MEturquoise module was found to be significantly related to hypertension and the MEbrown module was significantly related to the history of other malignancies. Functional enrichment analysis showed that the MEturquoise module was associated with the GO biological process terms of transcription from RNA polymerase II promoter, positive regulation of male gonad development, endocardial cushion development, and endothelial cell differentiation. The MEbrown module was associated with GO terms DNA binding, epithelial-to-mesenchymal transition, and transcription from RNA polymerase II promoter. A total of 10 hub genes were identified and validated at transcriptional and translational levels. Conclusions: The identified ceRNAs may play a critical role in the progression and metastasis of EC and are thus candidate therapeutic targets and potential prognostic biomarkers. The two modules constructed further provide a useful reference that will advance understanding of the mechanisms of tumorigenesis in EC.