Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer

Abstract Background The underlying circular RNAs (circRNAs)-related competitive endogenous RNA (ceRNA) mechanisms of pathogenesis and prognosis in non-small cell lung cancer (NSCLC) remain unclear. Methods Differentially expressed circRNAs (DECs) in two Gene Expression Omnibus datasets (GSE101684 an...

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Main Authors: Jia Yang, Ran Hao, Yunlong Zhang, Haibin Deng, Wenjing Teng, Zhongqi Wang
Format: Article
Language:English
Published: BMC 2021-11-01
Series:Cancer Cell International
Subjects:
Online Access:https://doi.org/10.1186/s12935-021-02278-z
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author Jia Yang
Ran Hao
Yunlong Zhang
Haibin Deng
Wenjing Teng
Zhongqi Wang
author_facet Jia Yang
Ran Hao
Yunlong Zhang
Haibin Deng
Wenjing Teng
Zhongqi Wang
author_sort Jia Yang
collection DOAJ
description Abstract Background The underlying circular RNAs (circRNAs)-related competitive endogenous RNA (ceRNA) mechanisms of pathogenesis and prognosis in non-small cell lung cancer (NSCLC) remain unclear. Methods Differentially expressed circRNAs (DECs) in two Gene Expression Omnibus datasets (GSE101684 and GSE112214) were identified by utilizing R package (Limma). Circinteractome and StarBase databases were used to predict circRNA associated-miRNAs and mRNAs, respectively. Then, protein–protein interaction (PPI) network of hub genes and ceRNA network were constructed by STRING and Cytoscape. Also, analyses of functional enrichment, genomic mutation and diagnostic ROC were performed. TIMER database was used to analyze the association between immune infiltration and target genes. Kaplan–Meier analysis, cox regression and the nomogram prediction model were used to evaluate the prognostic value of target genes. Finally, the expression of potential circRNAs and target genes was validated in cell lines and tissues by quantitative real-time PCR (qRT-PCR) and Human Protein Atlas (HPA) database. Results In this study, 15 DECs were identified between NSCLC tissues and adjacent-normal tissues in two GEO datasets. Following the qRT-PCR corroboration, 7 DECs (hsa_circ_0002017, hsa_circ_0069244, hsa_circ_026337, hsa_circ_0002346, hsa_circ_0007386, hsa_circ_0008234, hsa_circ_0006857) were dramatically downregulated in A549 and SK-MES-1 compared with HFL-1 cells. Then, 12 circRNA-sponged miRNAs were screened by Circinteractome and StarBase, especially, hsa-miR-767-3p and hsa-miR-767-5p were significantly up-regulated and relevant to the prognosis. Utilizing the miRDB and Cytoscape, 12 miRNA-target genes were found. Functional enrichment, genomic mutation and diagnostic analyses were also performed. Among them, FNBP1, AKT3, HERC1, COL4A1, TOLLIP, ARRB1, FZD4 and PIK3R1 were related to the immune infiltration via TIMER database. The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram. Furthermore, the hub-mRNAs were validated in cell lines and tissues. Conclusion We constructed the circRNA-miRNA-mRNA network that might provide novel insights into the pathogenesis of NSCLC and reveal promising immune infiltration and prognostic biomarkers.
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spelling doaj.art-7660cdea4443411ca9791a3d957712052022-12-21T19:22:13ZengBMCCancer Cell International1475-28672021-11-0121111710.1186/s12935-021-02278-zConstruction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancerJia Yang0Ran Hao1Yunlong Zhang2Haibin Deng3Wenjing Teng4Zhongqi Wang5Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineSchool of Nursing, Hebei Medical UniversityDepartment of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese MedicineDepartment of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineAbstract Background The underlying circular RNAs (circRNAs)-related competitive endogenous RNA (ceRNA) mechanisms of pathogenesis and prognosis in non-small cell lung cancer (NSCLC) remain unclear. Methods Differentially expressed circRNAs (DECs) in two Gene Expression Omnibus datasets (GSE101684 and GSE112214) were identified by utilizing R package (Limma). Circinteractome and StarBase databases were used to predict circRNA associated-miRNAs and mRNAs, respectively. Then, protein–protein interaction (PPI) network of hub genes and ceRNA network were constructed by STRING and Cytoscape. Also, analyses of functional enrichment, genomic mutation and diagnostic ROC were performed. TIMER database was used to analyze the association between immune infiltration and target genes. Kaplan–Meier analysis, cox regression and the nomogram prediction model were used to evaluate the prognostic value of target genes. Finally, the expression of potential circRNAs and target genes was validated in cell lines and tissues by quantitative real-time PCR (qRT-PCR) and Human Protein Atlas (HPA) database. Results In this study, 15 DECs were identified between NSCLC tissues and adjacent-normal tissues in two GEO datasets. Following the qRT-PCR corroboration, 7 DECs (hsa_circ_0002017, hsa_circ_0069244, hsa_circ_026337, hsa_circ_0002346, hsa_circ_0007386, hsa_circ_0008234, hsa_circ_0006857) were dramatically downregulated in A549 and SK-MES-1 compared with HFL-1 cells. Then, 12 circRNA-sponged miRNAs were screened by Circinteractome and StarBase, especially, hsa-miR-767-3p and hsa-miR-767-5p were significantly up-regulated and relevant to the prognosis. Utilizing the miRDB and Cytoscape, 12 miRNA-target genes were found. Functional enrichment, genomic mutation and diagnostic analyses were also performed. Among them, FNBP1, AKT3, HERC1, COL4A1, TOLLIP, ARRB1, FZD4 and PIK3R1 were related to the immune infiltration via TIMER database. The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram. Furthermore, the hub-mRNAs were validated in cell lines and tissues. Conclusion We constructed the circRNA-miRNA-mRNA network that might provide novel insights into the pathogenesis of NSCLC and reveal promising immune infiltration and prognostic biomarkers.https://doi.org/10.1186/s12935-021-02278-zcircRNAceRNA networkNon-small cell lung cancerImmune infiltrationPrognosis
spellingShingle Jia Yang
Ran Hao
Yunlong Zhang
Haibin Deng
Wenjing Teng
Zhongqi Wang
Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer
Cancer Cell International
circRNA
ceRNA network
Non-small cell lung cancer
Immune infiltration
Prognosis
title Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer
title_full Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer
title_fullStr Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer
title_full_unstemmed Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer
title_short Construction of circRNA-miRNA-mRNA network and identification of novel potential biomarkers for non-small cell lung cancer
title_sort construction of circrna mirna mrna network and identification of novel potential biomarkers for non small cell lung cancer
topic circRNA
ceRNA network
Non-small cell lung cancer
Immune infiltration
Prognosis
url https://doi.org/10.1186/s12935-021-02278-z
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