Oncology Letters · 10 authors, 2 centres
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This study analyzed transcriptomic data and performed laboratory experiments to show that expression of HPV18 E6E7 oncogenes inhibits multiple cell death pathways, including apoptosis, autophagy, and pyroptosis, in esophageal squamous cell carcinoma cells.
The study used transcriptomic analysis of RNA-Seq data from HPV18-positive and -negative esophageal squamous cell carcinoma (ESCC) samples to identify differentially expressed genes. These genes were found to be enriched in cell death pathways, including apoptosis, pyroptosis, and autophagy. Experimental verification was conducted using ESCC cell lines, including HPV-negative KYSE150 and KYSE180 cells engineered to express HPV18 E6E7, and HPV-positive EC109 and EC9706 cells. Functional assays demonstrated that HPV18 E6E7 inhibited cisplatin-induced apoptosis, blocked autophagosome-lysosome fusion to inhibit autophagy, and suppressed α-ketoglutarate-induced pyroptosis, potentially via GSDMC inhibition. The study concludes that HPV18 E6E7 inhibits multiple cell death modes, which may contribute to ESCC carcinogenesis. Limitations include the use of in vitro cell line models and the need for further validation, such as HPV18 E6E7 knockout experiments in HPV-positive cells.
