Targeting RASL12 by miR-6791-5p fuels malignant progression in lung adenocarcinoma.

BACKGROUND

Lung adenocarcinoma (LUAD) poses significant clinical challenges due to its heterogeneity and metastatic potential, necessitating deeper molecular characterization. This study investigated the role of miR-6791-5p and its target RASL12 in LUAD progression.

METHODS

Expression profiles and prognostic relevance were analyzed in 203 LUAD patients, cell lines, and public databases. Biological functions were evaluated through CCK-8, Transwell, independent RASL12 knockdown, and rescue assays. Interactions were validated by dual-luciferase assays. Downstream pathways were explored via Gene Set Enrichment Analysis (GSEA).

RESULTS

miR-6791-5p was significantly upregulated in LUAD (p < 0.001), independently predicting poor overall survival (HR = 2.411, p = 0.003). Functionally, miR-6791-5p promoted LUAD cell proliferation, migration, and invasion. RASL12 was confirmed as a direct target, exhibiting decreased mRNA and protein expression in tumors that negatively correlated with miR-6791-5p. Independent RASL12 knockdown enhanced tumor aggressiveness, while its co-knockdown partially reversed the tumor-suppressive effects of miR-6791-5p inhibition. GSEA linked this axis to cell adhesion signaling dynamics.

CONCLUSIONS

miR-6791-5p acts as an oncogene in LUAD by directly targeting the tumor suppressor RASL12. This axis modulates malignant phenotypes, representing a promising prognostic biomarker and potential therapeutic candidate.