Pei Yan, Lin Kang
Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, Jiangsu, 210006, China.
BMC Med Genomics. 2025 Jul 10;18(1):115. doi: 10.1186/s12920-025-02182-9.
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.
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.
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.
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.
对于肺腺癌（LUAD），由环状RNA（circRNA）介导的竞争性内源性RNA（ceRNA）网络已部分构建。然而，仍有大量网络需要深入研究，以揭示LUAD中的新型调控轴。
从公开数据库中获取临床信息和转录组数据。通过逐层筛选和验证构建circRNA介导的ceRNA子网和风险评分。通过CIBERSORT进行免疫浸润分析。定量实时PCR、免疫组织化学分析和双荧光素酶报告基因检测证实了枢纽基因的表达及其关系。
9种circRNA、81种miRNA和952种mRNA在LUAD组织中的表达存在显著差异。随后，利用63个miRNA-mRNA相互作用和3个circRNA-miRNA相互作用生成了一个ceRNA网络。经过枢纽基因筛选和生存分析，获得了由hsa_circ_0072088和hsa_circ_0049271介导的两个预后子网。然后，成功构建了由MMP14和DCN组成的风险评分，并使用不同数据集进行了验证。在高风险组中，死亡人数更多，预后更差。高风险组和低风险组之间免疫浸润细胞的分布不同，且它们与DCN和MMP14的表达以及风险评分均相关。
两个关键调控轴，即hsa_circ_0072088/hsa-miR-532-3p/MMP14和hsa_circ_0049271/hsa-miR-224-5p/DCN，可能参与了LUAD的致癌过程、预后及免疫浸润。
