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Construction of Endometrial Carcinoma ceRNA Network and Screening of Key Genes Based on TCGA Database
Yuchun Song1, Ping Chu1, Pan Li1
1Department of Gynecology and Obstetrics, Yantai Affiliated Hospital of Binzhou Medical University, Muping District, Yantai, Shandong 264100, China.
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.
Insights
This study identifies a novel long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network in endometrial cancer. This network, including specific lncRNA, miRNA, and mRNA targets, offers potential biomarkers and therapeutic strategies for endometrial cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in human tumor development.
- Understanding the complex regulatory networks involving lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) is crucial for advancing endometrial cancer research.
Purpose of the Study:
- To elucidate the lncRNA-miRNA-mRNA regulatory network in endometrial cancer.
- To identify potential diagnostic biomarkers and therapeutic targets within this network.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) data for miRNA, mRNA, and lncRNA expression profiling.
- Employed differential expression analysis (DESeq2), ceRNA network construction, and bioinformatics tools (STRING, Cytoscape) for network and hub gene identification.
- Validated key findings using the StarBase database and RT-qPCR.
Main Results:
- Identified significant differential expression of 14 lncRNAs, 65 miRNAs, and 1119 mRNAs in endometrial cancer.
- Constructed a ceRNA network revealing key regulatory interactions and identified 10 hub genes.
- Discovered a specific lncRNA-miRNA-mRNA axis (CTD-2314B22, RP11-89K21/hsa-miR-143, hsa-miR-424/LEFTY1, LIN28A, LHX3, ST8SIA3, CEP55) associated with endometrial cancer progression and patient survival.
Conclusions:
- The identified lncRNA-miRNA-mRNA network provides novel insights into endometrial cancer pathogenesis.
- Specific components of this network, such as the CTD-2314B22/hsa-miR-424/LEFTY1 axis, represent promising biomarkers and therapeutic targets for endometrial cancer.
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