ArticleFrontiers in genetics2026
The role of miRNAs in the development of brain metastases originating from lung adenocarcinoma.
Article in Frontiers in genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Brain metastases (BMs) represent most malignant lesions of the central nervous system. Lung cancer-particularly lung adenocarcinoma (LUAD, ∼25%)-is the most common source of BMs. MicroRNAs (miRNAs) play a crucial role in regulating gene expression, thereby contributing to tumor progression and metastatic spread. Identifying these regulatory molecules may enable a deeper understanding of the mechanisms driving LUAD brain metastasis (LUAD-BM) development and reveal therapeutic targets to prevent or limit disease progression. Methods: Next-generation RNA sequencing (RNA-seq) was performed on six LUAD-BM and six non-tumorous human brain tissue samples to assess miRNA expression profiles. Additionally, RNA-seq data from 20 primary LUAD and 15 normal lung tissue samples were obtained from The Cancer Genome Atlas (TCGA) database. MiRNAs showing the most pronounced alterations in LUAD-BM samples were selected for validation by real time quantitative polymerase chain reaction (RT-qPCR). Results: Analysis of RNA-seq data identified 229 differentially expressed (DE) miRNAs between LUAD-BM and control samples. Functional annotation analysis indicated that these DE miRNAs are key regulators of tumorigenesis and metastasis. Using the Mann-Whitney U test, ten miRNAs were confirmed to differ significantly between LUAD-BM and normal brain tissue. Receiver operating characteristic (ROC) curve analysis demonstrated their diagnostic potential. Among the ten validated miRNAs, miR-200c-3p, miR-146b-5p, and miR-3934-5p showed distinct expression patterns between primary LUAD and LUAD-BM, while miR-10a-5p, miR-210-3p, and miR-130b-3p exhibited stepwise dysregulation along the normal lung-LUAD-LUAD-BM axis, suggesting their involvement in metastatic progression. Conclusion: We identified ten miRNAs that showed preliminary ability to differentiate LUAD-BM from normal brain tissue. These findings indicate possible diagnostic and therapeutic implications. Among these, six miRNAs showed significant expression changes along the normal control-primary LUAD-LUAD-BM axis, highlighting their potential as biomarkers and therapeutic targets in BM development.
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