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...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s12920-025-02182-9 |
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| 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 |
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| institution | DOAJ |
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| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| 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 |