Human papillomavirus type 18 oncoproteins exert their oncogenicity in esophageal and tongue squamous cell carcinoma cell lines distinctly

Abstract

BackgroundIncreasing evidence indicates an etiological role of human papillomavirus (HPV) in head and neck cancers, particularly oropharyngeal squamous cell carcinoma (OPSCC). However, the association between HPV and other cancers, including esophageal and tongue remains unclear. This study delineated the molecular characteristics of HPV18 E6 and E7 in esophageal (EC109 and EC9706) and tongue (Tca83) cancer cell lines with reference to cervical cancer (HeLa).MethodsWe analysed the HPV transcription profiles of esophageal and tongue cancer cells through Next-generation RNA sequencing, and the role of HPV18 E6 and E7 in these cells was assessed via siRNA approach, Western blotting and immunofluorescence assays.ResultsOverall, the HPV transcription profiles of esophageal and tongue cancer cells mimicked that of cervical cancer cells, with notable disruption of E2, and expression of E6, spliced E6 (E6*), E7, E1 and L1 transcripts. As with cervical cancer cells, p53 and its downstream transactivation target, p21, were found to be the major targets of E6 in esophageal and tongue cancer cell lines. Intriguingly, E7 preferentially targeted p130 in the two esophageal cancer cell lines, instead of pRb as in cervical cancer. Tca83 exhibited an E7 to E6 transcript ratio comparable to HeLa (cervix), targeted the ERK1/2 and MMP2 pathways, and was dependent on E6 and E7 to survive and proliferate. In contrast, both the esophageal cancer cell lines were distinct from HeLa in these aspects.ConclusionsThis is the first study that delineates transcript expression and protein interaction of HPV18 E6 and E7 in esophageal and tongue cancer cell lines, suggesting that HPV plays a role in inducing these cancers, albeit via distinct pathways than those observed in cervical cancer.

Single-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and transcriptional activities of ECs in CC

“…8 Previous gene expression studies from bulk transcriptional data have largely revealed transcriptional variation that may affect prognosis. 9 However, one of the major limitations is that bulk sequencing of tumor samples is unable to identify small subsets of tumor tissues. As a revolutionary method, single-cell RNA sequencing (scRNA-seq) has been widely used in various fields to dissect cellular compositions and characterize molecular properties of complex tissues.…”

E6-Encoded by Cancer-Causing Human Papillomavirus Interacts with Aurora Kinase A To Promote HPV-Mediated Carcinogenesis

“…This assay is carried out as described previously ( 29 ). Approximately 2 × 10 5 U-2 OS cells were plated onto coverslips.…”

Infection with Human Papillomavirus 18 Promotes Alkylating Agent-Induced Malignant Transformation in a Human Esophageal Cell Line

“…Epidemiological surveys have proven that nitrosamines and their precursors may increase the risk of EC. − This research suggests that the aforementioned risk factors are probably involved in the development or the progression of EC. In addition, HPV could play an etiological role in EC in the presence of other essential cofactors such as environmental and genetic predisposition . Previously, we found that nitrosamines exposure is involved in the carcinogenesis of esophageal epithelia in the high incidence area of Huai’an …”

“…In addition, HPV could play an etiological role in EC in the presence of other essential cofactors such as environmental and genetic predisposition. 17 Previously, we found that nitrosamines exposure is involved in the carcinogenesis of esophageal epithelia in the high incidence area of Huai'an. 18 N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG) is an environmental pollutant with high carcinogenicity and mutagenicity and is a synthetic N-nitroso compound used to replace nitrosamine compounds in nature to study its role in tumor formation.…”