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

IF 2.1 4区医学 Q3 GENETICS & HEREDITY

BMC Medical Genomics Pub Date : 2025-07-10 DOI:10.1186/s12920-025-02182-9

Yan Pei, Kang Lin

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引用次数: 0

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.

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综合分析揭示了环rna介导的与肺腺癌预后和免疫浸润相关的关键调控轴。

背景：对于肺腺癌（LUAD），环状RNA （circRNAs）介导的竞争性内源性RNA （ceRNA）网络已经部分构建。然而，仍然需要对大量的网络进行彻底的研究，以发现LUAD中新的调控轴。方法：从开放数据库中获取临床资料及转录组数据。通过层层筛选和验证，构建circrna介导的ceRNA子网和风险评分。免疫浸润分析采用CIBERSORT。实时荧光定量PCR、免疫组织化学分析和双荧光素酶报告基因分析证实了枢纽基因的表达及其相互关系。结果：LUAD组织中9个circrna、81个mirna和952个mrna的表达显著变化。随后，利用63个miRNA-mRNA相互作用和3个circRNA-miRNA相互作用构建ceRNA网络。通过枢纽基因筛选和生存分析，获得了hsa_circ_0072088和hsa_circ_0049271介导的两个预后子网络。然后，成功构建由MMP14和DCN组成的风险评分，并使用不同的数据集进行验证。高危组死亡较多，预后较差。免疫浸润细胞分布在高危组和低危组之间存在差异，且与DCN、MMP14表达及风险评分相关。结论：两个关键调控轴hsa_circ_0072088/hsa-miR-532-3p/MMP14和hsa_circ_0049271/hsa-miR-224-5p/DCN可能参与LUAD的癌变、预后和免疫浸润。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Medical Genomics 医学-遗传学

CiteScore

3.90

自引率

0.00%

发文量

243

审稿时长

3.5 months

期刊介绍： BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.