Transcriptomic analysis of the effects of the HPV18 E6E7 gene on the cell death mode in esophageal squamous cell carcinoma.

Abstract

Human papillomavirus (HPV) infection is one of the main causes of esophageal carcinoma (ESCA), and its carcinogenic mechanisms in ESCA require further investigation. E6 and E7 are HPV oncogenes, and their genomic integration is a crucial reason for the transformation of host cells into cancer cells. In order to reveal the role of oncogenes E6 and E7 in ESCA cells, the RNA-Seq raw data for HPV18-positive and -negative esophageal squamous cell carcinoma (ESCC) samples derived from the NCBI BioProject database were analyzed, and the differentially expressed genes were identified. Moreover, differentially expressed genes were enriched significantly in multiple cell death pathways, including apoptosis (cyclin-dependent kinase inhibitor 2A, plakophilin 1 and desmoglein 3), pyroptosis (gasdermin A, gasdermin C, NLR family pyrin domain containing 3, absent in melanoma 2, NLR family pyrin domain containing 1 and Toll like receptor 1) and autophagy (Unc-51 like autophagy activating kinase 1, adrenoceptor beta 2). Consequently, the effects of cisplatin-induced apoptosis and Hank's balanced salt solution-induced autophagy, and α-ketoglutarate-induced pyroptosis in the ESCC-expressing E6 and E7 cells were verified. Therefore, the expression of E6E7 may culminate in the inhibition of multiple cell death modes, which may also be one of the mechanisms of oncogene-induced carcinogenesis.