HERV6196 as an enhancer with oncogenic potential in rectal cancer

Colorectal cancer (CRC) is among the most prevalent malignancies. However, the regulatory networks involved in tumor occurrence and development are still poorly understood. Human endogenous retroviruses (HERVs), a class of transposable elements, have been implicated in the development and progression of various human cancers. This study presents the first comprehensive locus-specific profiling of the expression of HERV gene transcripts in rectal cancer, revealing significantly dysregulated HERVs. Analysis of data from three Gene Expression Omnibus data sets revealed 25 upregulated HERVs and 7 downregulated HERVs. Dysregulation of HERV6196, a type of HERVH, was validated through reverse transcription quantitative PCR and droplet digital PCR in cells and tissues. Additionally, HERV6196 promoted the proliferation, inhibited the apoptosis, enhanced the colony formation ability, and enhanced the migration capability of rectal cancer cells. Moreover, HERV6196 functioned as an enhancer, promoting the expression of neighboring genes and the development of CRC. In summary, the present results revealed that HERV6196 is involved in the pathogenesis of rectal cancer, indicating the potential contribution of dysregulated HERVs to the development and progression of CRC through gene expression modulation.IMPORTANCEThe role of human endogenous retroviruses (HERVs) in colorectal cancer (CRC) remains insufficiently understood. The present study revealed aberrant expression of HERV gene transcripts in cancerous tissues compared with non-cancerous tissues. HERV6196 contributes to CRC progression by regulating the expression of neighboring genes. These findings suggest that HERVs may serve as enhancers and regulate oncogenic gene expression, providing new insights for rewiring transcriptional regulatory networks in CRC pathogenesis.