Integrated analysis reveals key circRNA-mediated regulatory axes related to prognosis and immune infiltration in lung adenocarcinoma

Abstract Background For lung adenocarcinoma (LUAD), the competitive endogenous RNA (ceRNA) networks mediated by circular RNAs (circRNAs) have been partially constructed. However, a mass of networks still need to be thoroughly investigated to uncover novel regulatory axes in LUAD. Methods Clinical in...

Full description

Saved in:
Bibliographic Details
Main Authors: Yan Pei, Kang Lin
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Medical Genomics
Subjects:
Online Access:https://doi.org/10.1186/s12920-025-02182-9
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849738146064891904
author Yan Pei
Kang Lin
author_facet Yan Pei
Kang Lin
author_sort Yan Pei
collection DOAJ
description Abstract Background For lung adenocarcinoma (LUAD), the competitive endogenous RNA (ceRNA) networks mediated by circular RNAs (circRNAs) have been partially constructed. However, a mass of networks still need to be thoroughly investigated to uncover novel regulatory axes in LUAD. Methods Clinical information along with transcriptome data were obtained from open databases. The circRNA-mediated ceRNA subnetworks and a risk score were constructed through layer-by-layer screening and validating. Immune infiltration analysis was performed by CIBERSORT. Quantitative real-time PCR, immunohistochemical analysis, and dual-luciferase reporter assays confirmed the expression and relationships of hub genes. Results The expression of 9 circRNAs, 81 miRNAs, and 952 mRNAs significantly varied in LUAD tissues. Subsequently, 63 miRNA-mRNA interactions and 3 circRNA-miRNA interactions were employed to generate a ceRNA network. Two prognostic subnetworks mediated by hsa_circ_0072088 and hsa_circ_0049271 were obtained following hub genes screening and survival analysis. Then, a risk score consisting of MMP14 and DCN was successfully constructed and verified using a different dataset. Among the high-risk group, more deaths and poor prognosis occurred. The distribution of immune infiltrating cells varied between high- and low-risk groups, and they were correlated with both the expression of DCN and MMP14 and the risk score. Conclusions The two key regulatory axes, hsa_circ_0072088/hsa-miR-532-3p/MMP14 and hsa_circ_0049271/hsa-miR-224-5p/DCN, might be involved in carcinogenesis, prognosis and immune infiltration of LUAD.
format Article
id doaj-art-186130b00bc24a14beed45b2817c22b2
institution DOAJ
issn 1755-8794
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series BMC Medical Genomics
spelling doaj-art-186130b00bc24a14beed45b2817c22b22025-08-20T03:06:43ZengBMCBMC Medical Genomics1755-87942025-07-0118111610.1186/s12920-025-02182-9Integrated analysis reveals key circRNA-mediated regulatory axes related to prognosis and immune infiltration in lung adenocarcinomaYan Pei0Kang Lin1Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical UniversityDepartment of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical UniversityAbstract Background For lung adenocarcinoma (LUAD), the competitive endogenous RNA (ceRNA) networks mediated by circular RNAs (circRNAs) have been partially constructed. However, a mass of networks still need to be thoroughly investigated to uncover novel regulatory axes in LUAD. Methods Clinical information along with transcriptome data were obtained from open databases. The circRNA-mediated ceRNA subnetworks and a risk score were constructed through layer-by-layer screening and validating. Immune infiltration analysis was performed by CIBERSORT. Quantitative real-time PCR, immunohistochemical analysis, and dual-luciferase reporter assays confirmed the expression and relationships of hub genes. Results The expression of 9 circRNAs, 81 miRNAs, and 952 mRNAs significantly varied in LUAD tissues. Subsequently, 63 miRNA-mRNA interactions and 3 circRNA-miRNA interactions were employed to generate a ceRNA network. Two prognostic subnetworks mediated by hsa_circ_0072088 and hsa_circ_0049271 were obtained following hub genes screening and survival analysis. Then, a risk score consisting of MMP14 and DCN was successfully constructed and verified using a different dataset. Among the high-risk group, more deaths and poor prognosis occurred. The distribution of immune infiltrating cells varied between high- and low-risk groups, and they were correlated with both the expression of DCN and MMP14 and the risk score. Conclusions The two key regulatory axes, hsa_circ_0072088/hsa-miR-532-3p/MMP14 and hsa_circ_0049271/hsa-miR-224-5p/DCN, might be involved in carcinogenesis, prognosis and immune infiltration of LUAD.https://doi.org/10.1186/s12920-025-02182-9circRNAceRNA networkPrognosisImmune infiltrationLung adenocarcinoma
spellingShingle Yan Pei
Kang Lin
Integrated analysis reveals key circRNA-mediated regulatory axes related to prognosis and immune infiltration in lung adenocarcinoma
BMC Medical Genomics
circRNA
ceRNA network
Prognosis
Immune infiltration
Lung adenocarcinoma
title Integrated analysis reveals key circRNA-mediated regulatory axes related to prognosis and immune infiltration in lung adenocarcinoma
title_full Integrated analysis reveals key circRNA-mediated regulatory axes related to prognosis and immune infiltration in lung adenocarcinoma
title_fullStr Integrated analysis reveals key circRNA-mediated regulatory axes related to prognosis and immune infiltration in lung adenocarcinoma
title_full_unstemmed Integrated analysis reveals key circRNA-mediated regulatory axes related to prognosis and immune infiltration in lung adenocarcinoma
title_short Integrated analysis reveals key circRNA-mediated regulatory axes related to prognosis and immune infiltration in lung adenocarcinoma
title_sort integrated analysis reveals key circrna mediated regulatory axes related to prognosis and immune infiltration in lung adenocarcinoma
topic circRNA
ceRNA network
Prognosis
Immune infiltration
Lung adenocarcinoma
url https://doi.org/10.1186/s12920-025-02182-9
work_keys_str_mv AT yanpei integratedanalysisrevealskeycircrnamediatedregulatoryaxesrelatedtoprognosisandimmuneinfiltrationinlungadenocarcinoma
AT kanglin integratedanalysisrevealskeycircrnamediatedregulatoryaxesrelatedtoprognosisandimmuneinfiltrationinlungadenocarcinoma