Zuo Haiwei, Li Xia, Zheng Xixi, Sun Qiuwen, Yang Qianqian, Xin Yong
School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, China.
Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Front Genet. 2021 Jul 7;12:673501. doi: 10.3389/fgene.2021.673501. eCollection 2021.
The growing evidence suggests 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 two circRNAs, two miRNAs, and two mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the five 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.
越来越多的证据表明，环状RNA（circRNAs）与肿瘤的发生和进展密切相关，然而circRNAs在肺腺癌（LUAD）中的调控机制仍不清楚。本研究阐明了circRNAs在LUAD中潜在的调控网络和功能机制。环状RNA、微小RNA（miRNAs）和信使RNA（mRNAs）的表达数据从基因表达综合数据库（GEO）中获取。基于GSE101586、GSE101684和GSE112214，我们鉴定出差异表达的环状RNA（DEcircRNAs）。分别依据GSE135918和GSE32863，我们筛选出差异表达的微小RNA（DEmiRNAs）和信使RNA（DEmRNAs）。然后，构建了一个与LUAD相关的新型竞争性内源RNA（ceRNA）调控网络。我们还揭示了这些DEcircRNAs调控的生物学过程和信号通路。基于癌症基因组图谱（TCGA）和GEO中LUAD患者的基因表达数据和生存信息，我们进行了生存分析以选择与预后相关的DEmRNAs，并构建了一个新的circRNA-miRNA-mRNA核心调控网络。同时，利用定量实时聚合酶链反应（qRT-PCR）验证ceRNA核心调控网络中的DEcircRNAs。结果，共鉴定出8个DEcircRNAs、19个DEmiRNAs和85个DEmRNAs。新型ceRNA调控网络包括5个circRNAs、8个miRNAs和22个mRNAs。最终的ceRNA核心调控网络包含2个circRNAs、2个miRNAs和2个mRNAs。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，这5个DEcircRNAs可能通过Wnt信号通路和Hippo信号通路影响LUAD的发生和进展。总而言之，本研究揭示了LUAD中circRNA相关ceRNAs的调控网络和功能机制。
