Integrated WGCNA of lncRNA-mRNA Networks Identifies Novel Hub Genes and Potential Therapeutic Agents for Liver Cirrhosis via Molecular Docking Validation

Liver cirrhosis (LC) is a complex pathological condition characterized by extensive transcriptomic reprogramming, yet the regulatory role of non-coding RNAs in disease progression remains poorly understood. This study aimed to systematically investigate long non-coding RNA (lncRNA)-messenger RNA (mRNA) interaction networks in LC through weighted gene co-expression network analysis (WGCNA). Gene expression profiles from datasets GSE197406, GSE107170, and GSE17548 were retrieved from the Gene Expression Omnibus (GEO) database, and differentially expressed lncRNAs and mRNAs were identified. Co-expression modules were constructed using WGCNA. Furthermore, functional enrichment analyses were conducted and drug repurposing opportunities were evaluated. Additionally, lncRNA-mRNA co-expression networks and lncRNA-mRNA-pathway networks were constructed to identify key regulatory relationships. Molecular docking simulations were subsequently performed to validate potential drug-target interactions. The results revealed several co-expression modules significantly associated with LC, particularly the turquoise module (r = 0.81). Genes within this module were enriched in several biological pathways, including the PI3K-Akt signaling pathway, NF-κB signaling pathway, and chemokine signaling pathway. The hub lncRNA in the turquoise module, NONHSAT134945.2, was found to be co-expressed with mRNAs involved in inflammasome-mediated pyroptosis and hepatocyte activation, such as CSF1R, HCK, and CASP1. Based on this hub gene signature, AB-1010, GW768505A, and Dasatinib were identified as potential therapeutic candidates. Molecular docking analysis confirmed that these compounds exhibit high binding affinity to CSF1R and HCK, with all interatomic distances maintained below 3.5 Å. These findings provide new insights into the molecular mechanisms underlying LC and suggest that the NONHSAT134945.2-CSF1R/HCK axis may serve as a valuable target for future translational research and therapeutic development.