Is cross-species horizontal gene transfer responsible for gallbladder carcinogenesis

Abstract Background: Cross-species horizontal gene transfer (HGT) involves the transfer of genetic material between different species of organisms. In recent years, mounting evidence has emerged that cross-species HGT does take place and may play a role in the development and progression of diseases. Methods: Transcriptomic data obtained from patients with gallbladder cancer (GBC)was assessed for the differential expression of antisense RNAs (asRNAs). Cross-species blast analysis was performed with viral, bacterial, fungal, and ancient human genomes to elucidate the evolutionary cross species origins of these differential asRNAs. Functional enrichment analysis and text mining were conducted and a network of asRNAs targeting mRNAs was constructed to understand the function of differential asRNAs better. Results: A total of 17 differentially expressed antisense RNAs (asRNAs) were identified in gallbladder cancer tissue. BLAST analysis of 15 of these asRNAs (AFAP1-AS1, HMGA2-AS1, MNX1-AS1, SLC2A1-AS1, BBOX1-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1-AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS) showed varying degree of similarities with bacterial and viral genomes, except for UNC5B-AS1 and SOX21-AS1, which were conserved during evolution. Two of these asRNAs (VPS9D1-AS1 and SLC2A1-AS1) exhibited a high degree of similarity with viral genomes including (Chikungunya virus, Human immunodeficiency virus 1, Stealth virus 1, and Zika virus) and bacterial genomes including ( Staphylococcus sp., Bradyrhizobium sp., Pasteurella multocida sp., and , Klebsiella pneumoniae sp .), indicating potential HGT during evolution. Conclusion: The results provide novel evidence supporting the hypothesis that differentially expressed asRNAs in GBC exhibit varying sequence similarity with bacterial, viral, and ancient human genomes, indicating a potential shared evolutionary origin. These non-coding genes are enriched with methylation and were found to be associated with cancer-related pathways, including the P53 and PI3K-AKT signaling pathways, suggesting their possible involvement in tumor development.