Introduction Human endogenous retroviruses (HERVs) are suggested to be involved in the development of certain diseases, especially cancers. In pancreatic cancer cells, shRNA-mediated downregulation of HERV-K env RNA decreases cell proliferation and tumor growth through the RAS-ERK-RSK pathway; in colorectal cancer, CRISPR-Cas9 knockout (KO) of the HERV-K env gene affects tumorigenic characteristics through the nupr-1 gene.

Methods To elucidate the function of HERV-K Env protein in cancers, HERV-K env gene was knocked out using CRISPR-Cas9 in ovarian cancer cell lines SKOV3 and OVCAR3. Tumorigenic features like cell proliferation, migration, and invasion were analyzed, as well as related protein expression via western blotting. Gene expression patterns were evaluated using next-generation mRNA sequencing and gene ontology and pathway analyses.

Results After HERV-K env gene KO, RNA and protein expression significantly decreased, and tumorigenic features like cell proliferation, migration, and invasion significantly reduced. RB protein expression significantly increased in HERV-K env KO SKOV3 cells, while phospho-RB protein decreased in OVCAR3 cells. Transcriptome analysis showed significant differences in 37 DEGs out of 4,325 DEGs. SKOV3 cells had 31 upregulated and 32 downregulated DEGs, mainly related to RNA splicing, aging, and angiogenesis genes. OVCAR3 cells had 226 upregulated and 1,464 downregulated DEGs, mainly related to RNA splicing and aging genes.

Conclusion/Implications The results of this study showed that HERV-K env gene KO affects cell proliferation, invasion, and migration of ovarian cells through RB and Cyclin B1 proteins, but the specific regulation pattern can differ by cell line.