Human long non-coding RNAs acquired from bacteria via horizontal gene transfer promote gallbladder cancer.

Abstract

Background: Gallbladder cancer, the most common malignancy of the bile duct, has a poorly understood etiopathogenesis. Non-coding RNAs are implicated in various cancers, but their role in gallbladder carcinogenesis remains unclear.

Methods: Transcriptomic data from gallbladder cancer patients were analyzed to identify differentially expressed long non-coding RNAs (lncRNAs). These data underwent cross-species phylogenetic analysis and BLAST comparison with bacterial and ancient human genomes, including Homo heidelbergensis and Homo neanderthalensis. Pathway analysis, gene-gene interactions, and data and text mining were performed for non-conserved, non-coding genes.

Results: Of 16 differentially expressed lncRNAs, seven showed phylogenetic links to bacterial genomes, suggesting acquisition through horizontal gene transfer (HGT) during human evolution. These lncRNAs were present in ancient human species with sequence variations. Functional analysis revealed their role in regulating biological and genetic processes, potentially promoting gallbladder carcinogenesis.

Conclusions: This is the first study to propose that seven human lncRNAs, likely of bacterial origin, were acquired through HGT during evolution. These lncRNAs regulate transcriptional and post-transcriptional processes, potentially inducing gallbladder carcinogenesis, thus highlighting a novel link between evolutionary genetics and cancer.