The role of miR-21 in early-stage lung adenocarcinoma: clinical and bioinformatics insights

Lung adenocarcinoma (LUAD) is one of the most common types of lung cancer and a leading cause of cancer-related mortality worldwide. This study aimed to identify key microRNAs (miRNAs) and genes involved in LUAD pathogenesis. We enrolled 50 patients diagnosed with early-stage LUAD between October 2021 and September 2023 as the observation group, along with 50 healthy individuals as the control group. Peripheral blood samples (5 mL) were collected from each participant for exosome isolation and quantitative analysis of miR-21. The results demonstrated that miR-21 expression was significantly higher in the observation group compared to the control group (P < 0.05). To further explore the molecular mechanisms underlying LUAD, publicly available RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) datasets were analyzed using bioinformatics approaches. Differential expression analysis of The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) datasets identified 296 differentially expressed miRNAs (192 upregulated, 104 downregulated) and 2942 differentially expressed genes (1691 upregulated, 1251 downregulated). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that miR-21 target genes are involved in critical biological processes, including cell proliferation, apoptosis, and signal transduction. A protein-protein interaction (PPI) network analysis revealed key protein modules associated with LUAD progression.Immunohistochemistry (IHC) confirmed the high expression of miR-21 target genes IL12A and TGFBI in LUAD tissues. Additionally, the interaction between miR-21 and long non-coding RNAs (lncRNAs) was explored, revealing complex regulatory networks. Gene co-expression analysis of the miR-21 target gene ZNF367 identified highly correlated genes associated with mitosis and DNA repair. Immune infiltration analysis using CIBERSORT demonstrated significant differences in immune cell composition between LUAD patients and healthy controls. Survival analysis further indicated that high miR-21 expression is associated with poorer prognosis, underscoring its potential as a prognostic biomarker.Furthermore, scRNA-seq provided insights into the dynamic molecular changes occurring during the transition from normal to malignant states. Collectively, these findings highlight the critical role of miR-21 in LUAD pathogenesis and suggest potential avenues for targeted therapies and personalized treatment strategies.