Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

Abstract

Objective. Long noncoding RNA (lncRNA) has received more and more attention in human tumor research. This study is aimed at clarifying the regulatory network of lncRNAs-microRNAs- (miRNAs-) mRNAs and at determining the relevant targets in the development of endometrial cancers. Methods. Download the miRNA, mRNA, and lncRNA expression profile data of endometrial cancer patients from TCGA; use the “DESeq2” package of R software to identify the differential expression of miRNAs, mRNAs, and lncRNAs; construct a network of ceRNA; and perform gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment assessment on mRNAs in the network of ceRNA; string and Cytoscape 3.7.2 perform PPI assessment on target genes and TOP 10 hub gene screening; Cytoscape 3.7.2 computer program was employed for constructing the lncRNA-miRNA-TOP10 hub mRNA network diagram to determine the signal axis; StarBase database to verify the Top10 hub mRNA expression; the “survival” package in R computer program was implemented to analyze the survival rate of all genes on the lncRNA-miRNA-Top10 hub mRNA network diagram; RT-qPCR to verify the expression level of genes on the signal axis. Results. 1119 differential mRNAs, 14 differential lncRNAs, and 65 differential miRNAs were screened in TCGA; we constructed a ceRNA regulatory network composed of 5 DELs, 7 DEMs, and 90 DEGs; String combined with Cytoscape to screen out Top10 hub genes, namely: LEFTY1, LIN28A, LHX3, ST8SIA3, CEP55, FBXO32, DCN, ANGPTL1, ADRA1A, and KCNMA1; the StarBase database verification results show that ADRA1A, ANGPTL1, FBXO32, KCNMA1, and DCN are downregulated in endometrial cancer tissues; LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer; the constructed lncRNA-miRNA-hub Top10 mRNA network map identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis; survival analysis results show that CTD-2314B22, RP11-89 K21, hsa-miR-96, hsa-miR-211, LHX3, ST8SIA3, and DCN are all related to survival; RT-qPCR results indicate CTD-2314B22, RP11-89 K21, LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 are upregulated in endometrial cancer cells, and hsa-miR-143 and hsa-miR-424 are downregulated in endometrial cancer cells. Conclusion. From the perspective of the lncRNA-miRNA-mRNA network, our study identified CTD-2314B22, RP11-89 K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55 signal axis, which can present considerably potent biomarkers and therapeutic targets for treating endometrial cancer.

Circulating miRNAs as a Tool for Early Diagnosis of Endometrial Cancer—Implications for the Fertility-Sparing Process: Clinical, Biological, and Legal Aspects

“…This work allowed identifying tens of these axes, with six of them carrying a high prognostic value. In the same year, Song and collaborators also took advantage of TGCA database to reconstruct a ceRNET including 5 deregulated lncRNA, 7 deregulated miR, and 90 deregulated mRNA [69]. In Figure 1, we report two simplified examples of ceRNET in EC.…”

The interplay of sex steroid hormones and microRNAs in endometrial cancer: current understanding and future directions

“…This network identifies 169 prognosis-associated RNAs, including 92 lncRNAs, 16 miRNAs, and 61 mRNAs (194). Several genes, such as ADRA1A, ANGPTL1, FBXO32, KCNMA1, DCN, LEFTY1, LIN28A, LHX3, ST8SIA3, and CEP55, are also regulated by the lncRNA-miRNA-mRNA network (195). Moreover, miRNA-mRNA regulatory networks are linked to the biological process of negative regulation of transcription from the RNA polymerase II promoter and positive regulation from the RNAD promoter (166).…”

Retracted: Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”