Multidimensional analysis of hsa-miR-140-3p and CKS1B correlation via the MAPK/ERK pathway in lung adenocarcinoma progression.

Cyclin-Dependent Kinase Subunit 1B (CKS1B) is significantly upregulated in lung adenocarcinoma (LUAD) tissues and is associated with poor clinical outcomes, such as shorter overall survival (OS) and progression-free survival (PFS). High CKS1B expression correlates with advanced tumor stage, aggressive pathology, and increased immune cell infiltration, indicating its role in modulating the tumor microenvironment and promoting immune evasion. We confirmed the elevated expression of CKS1B in LUAD cell lines through quantitative real-time polymerase chain reaction and Western blot analysis. Knockdown of CKS1B using small interfering RNA (siRNA) reduced cell proliferation, increased apoptosis, and impaired invasion. Additionally, CKS1B knockdown upregulated E-cadherin and downregulated N-cadherin, indicating suppression of epithelial-mesenchymal transition (EMT). We further demonstrated that CKS1B knockdown decreased the phosphorylation of MEK and ERK, suggesting inhibition of MAPK/ERK signaling. Bioinformatic analysis revealed that higher levels of hsa-miR-140-3p negatively correlate with CKS1B expression and are associated with improved survival outcomes, pointing to a potential tumor-suppressive axis. Decreased promoter methylation of CKS1B in LUAD tissues, along with its association with tumor mutation burden (TMB) and immune checkpoint expression, highlights its role in tumor progression and resistance to immunotherapy. A nomogram integrating CKS1B expression with clinical parameters effectively predicted 3- and 5-year survival probabilities, offering a tool for personalized risk assessment. In conclusion, our findings position CKS1B as a key factor in LUAD progression and suggest that targeting MAPK/ERK signaling could enhance the efficacy of immunotherapy and overcome chemoresistance.