WITHDRAWN: Integrated bioinformatics and experimental validation identify KLHL6 as a potential shared immune-related regulator linking idiopathic pulmonary fibrosis and major depressive disorder

Background Idiopathic pulmonary fibrosis (IPF) and major depressive disorder (MDD) are frequently comorbid conditions, yet their shared molecular mechanisms remain unclear. This study aimed to identify common key genes associated with both IPF and MDD through integrated multi-omics analysis and experimental validation. Methods GEO transcriptomic datasets were analyzed using differential expression analysis, weighted gene co-expression network analysis (WGCNA), and multiple machine-learning algorithms. Immune infiltration, gene set enrichment analysis (GSEA), and single-cell analyses were performed to investigate immune-related mechanisms. Clinical samples, in vitro experiments, molecular docking, and molecular dynamics simulations were used for validation. Results A total of 455 shared differential genes were identified, mainly enriched in immune-inflammatory pathways. KLHL6 was consistently upregulated in both IPF and MDD and demonstrated robust diagnostic performance. Single-cell analysis revealed KLHL6 enrichment in macrophages and microglia. KLHL6 knockdown attenuated fibrosis- and inflammation-related marker expression while restoring BDNF levels. Molecular docking suggested a favorable binding potential between Lycorine and KLHL6, and Lycorine alleviated disease-related phenotypes in vitro. Conclusion KLHL6 may represent a shared immune-inflammatory factor associated with both IPF and MDD, while Lycorine may exert protective effects partly through KLHL6-associated pathways.