AUTHOR=Torner Bernadett , Klekner Álmos , Balogh István , Penyige András , Géczi Dóra , Gáspár Tekla , Geszti Gréta , Birkó Zsuzsanna 
  
TITLE=The role of miRNAs in the development of brain metastases originating from lung adenocarcinoma
  
JOURNAL=Frontiers in Genetics
  
VOLUME=Volume 17 - 2026
  
YEAR=2026
  
URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2026.1769972
  
DOI=10.3389/fgene.2026.1769972
  
ISSN=1664-8021
  
ABSTRACT=IntroductionBrain 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.MethodsNext-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).ResultsAnalysis 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.ConclusionWe 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.