VAV2-associated ncRNA network in the focal adhesion pathway is dysregulated in laryngeal squamous cell carcinoma

BACKGROUND: The focal adhesion is a key pathway for cellular proliferation and migration. This study aimed to elucidate the function of VAV2, a key guanine nucleotide exchange factor in the focal adhesion pathway, and to investigate its post-transcriptional relationships through the predicted VAV2/miRNA/lncRNA network in Laryngeal Squamous Cell Carcinoma (LSCC). METHODS: RNA-seq data analysis from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets was performed using R software. Differential expression profiles of mRNAs, miRNAs, and lncRNAs were integrated with multi-database miRNA-target predictions to construct a high-confidence VAV2-associated ncRNA network. The RT-qPCR and Western blotting techniques were used to validate the gene analysis in 63 paired LSCC and adjacent normal tissues. RESULTS: Focal adhesion was among the significantly enriched pathways (47 genes, P = 2.23 × 10⁻⁴). VAV2 exhibited consistent upregulation at both mRNA and protein levels in tumor tissues (P < 0.0001). Tumor samples exhibited the downregulation of miR-449b-5p and miR-495-3p, along with pronounced significant overexpression of LINC00665 and CCDC144NL-AS1 (P < 0.01). Significant positive correlations were identified between VAV2 and lncRNAs (r = 0.76 and r = 0.79, P < 0.0001), alongside comparable negative correlations with miRNAs. CONCLUSION: Our results proposed that the predicted VAV2-associated ncRNA network might be involved in the focal adhesion pathway. These data suggested novel insights into the underlying mechanisms and hold promise as biomarkers and therapeutic targets.