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Published on: March 30, 2019
Identification of circRNA-miRNA-mRNA networks to explore underlying mechanism in lung cancer
Yajie Wang1, Yu Fu1
1Medical School, Kunming University of Science & Technology, #727 Jing Ming Nan Road, Chenggong County, Kunming, 650500 Yunnan China.
Background:
Circular RNAs (circRNAs) are involved in the occurrence and development of various tumors. CircRNAs can act as competing endogenous RNAs (ceRNAs), which are important regulatory networks, by regulating microRNAs (miRNAs). However, the effects of ceRNA networks on lung cancer (LC), especially the circRNA-miRNA-mRNA regulatory network, remain incompletely understood. Therefore, the aim of this study was to explore novel ceRNA networks and their function and underlying mechanisms in LC.
Methods:
Six RNA expression datasets were obtained from the Gene Expression Omnibus microarray datasets (circRNA: GSE158695, GSE101684, GSE112214, and GSE101586; miRNA: GSE135918; mRNA: GSE98929). First, we constructed a circRNA-miRNA-mRNA ceRNA network in LC using Cytoscape. Second, we constructed a protein-protein interaction network using STRING and identified hub genes using CytoHubba. Functional analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to predict the potential function of the hub genes. Third, expression and survival analysis of the hub genes were performed to identify prognostic genes.
Results:
We constructed a ceRNA network including 18 circRNAs, 32 miRNAs, and 135 mRNAs, and identified 10 hub genes (VEGFA, FOS, MAD2L1, CREBBP, TYMS, EDN1, RFC5, KIF11, SLC2A1, and TOP2A). Both GO and KEGG analyses revealed that the 10 hub genes were associated with several cancer‑related biological functions and pathways, including "oxygen levels", "nuclear division", and "HIF-1 signaling pathway". Five genes (MAD2L1, TYMS, KIF11, SLC2A1, and TOP2A) were associated with the prognosis of lung adenocarcinoma (LUAD), the most common histological type of LC.
Conclusion:
Our study provides novel insights into the pathogenesis and therapy of LC from a ceRNA network perspective.
Insights
This study reveals novel circular RNA-microRNA-messenger RNA networks in lung cancer (LC). Five key genes were identified as prognostic markers for lung adenocarcinoma, offering new therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Circular RNAs (circRNAs) play a role in tumor development and can function as competing endogenous RNAs (ceRNAs).
- The circRNA-microRNA-messenger RNA (miRNA-mRNA) regulatory network's role in lung cancer (LC) pathogenesis is not fully understood.
- Investigating these networks is crucial for understanding LC and developing targeted therapies.
Purpose of the Study:
- To explore novel circRNA-miRNA-mRNA ceRNA networks in lung cancer (LC).
- To identify key regulatory genes and pathways involved in LC development.
- To uncover potential prognostic biomarkers for lung adenocarcinoma (LUAD).
Main Methods:
- Utilized six RNA expression datasets from the Gene Expression Omnibus (GEO) for circRNA, miRNA, and mRNA.
- Constructed a circRNA-miRNA-mRNA ceRNA network using Cytoscape and identified hub genes.
- Performed protein-protein interaction network analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
Main Results:
- A comprehensive ceRNA network was built, comprising 18 circRNAs, 32 miRNAs, and 135 mRNAs.
- Ten hub genes were identified, including VEGFA, FOS, MAD2L1, CREBBP, TYMS, EDN1, RFC5, KIF11, SLC2A1, and TOP2A.
- Five hub genes (MAD2L1, TYMS, KIF11, SLC2A1, TOP2A) were significantly associated with the prognosis of lung adenocarcinoma (LUAD).
Conclusions:
- The study elucidates novel circRNA-miRNA-mRNA regulatory networks in lung cancer.
- Identified key hub genes and pathways, such as those related to oxygen levels and nuclear division, implicated in LC.
- The findings provide valuable insights into LC pathogenesis and potential therapeutic strategies targeting prognostic biomarkers.
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