AUTHOR=Zuo Haiwei , Li Xia , Zheng Xixi , Sun Qiuwen , Yang Qianqian , Xin Yong 

TITLE=A Novel circRNA–miRNA–mRNA Hub Regulatory Network in Lung Adenocarcinoma

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.673501

DOI=10.3389/fgene.2021.673501

ISSN=1664-8021

ABSTRACT=The growing evidences suggest that circular RNAs (circRNAs) have significant associations with tumor occurrence and progression, yet the regulatory mechanism of circRNAs in lung adenocarcinoma (LUAD) remains unclear. This study clarified the potentially regulatory network and functional mechanism of circRNAs in LUAD. The expression data of circRNAs, microRNAs (miRNAs) and messenger RNAs (mRNAs) were obtained from the Gene Expression Omnibus (GEO) database. Relying on GSE101586, GSE101684 and GSE112214, we identified differentially expressed circRNAs (DEcircRNAs). Depending on GSE135918 and GSE32863, we screened out differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs), respectively. Then, a novel competing endogenous RNA (ceRNA) regulatory network related to LUAD was constructed. We also revealed biological processes and signal pathways regulated by these DEcircRNAs. Based on gene expression data and survival information of LUAD patients in The Cancer Genome Atlas (TCGA) and GEO, we implemented survival analysis to select DEmRNAs related to prognosis, and build a novel circRNA-miRNA-mRNA hub regulatory network. Meanwhile, quantitative real-time PCR (qRT-PCR) was utilized to validate DEcircRNAs in the ceRNA hub regulatory network. As a result, a total of 8 DEcircRNAs, 19 DEmiRNAs and 85 DEmRNAs were identified. The novel ceRNA regulatory network included 5 circRNAs, 8 miRNAs and 22 mRNAs. The final ceRNA hub regulatory network contained 2 circRNAs, 2 miRNAs and 2 mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated the 5 DEcircRNAs may affect LUAD onset and progression through Wnt signaling pathway and Hippo signaling pathway. All in all, this study revealed the regulatory network and functional mechanism of circRNA-related ceRNAs in LUAD.