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.
Highlights
Increasing evidence indicates an etiological role of human papillomavirus (HPV) in head and neck cancers, oropharyngeal squamous cell carcinoma (OPSCC)
Esophageal and tongue cancer cell lines shared similar expression profile with cervical cancer cells, but exhibited different E7/E6 ratios Viral genome integration resulting in disruption and loss of viral transcripts are remarkable features of HPVmediated oncogenesis
HPV18 E6 in EC109, EC9706 and Tca83 targets p53 and its downstream targets in a similar manner Following the differential expression of HPV18 oncoproteins reported above, we examined whether E6 and E7 oncoproteins in esophageal (EC109 and EC9706) and tongue (Tca83) cancer cells target key cellular proteins in a similar manner to cervical cancer cells, such as HeLa
Summary
Increasing evidence indicates an etiological role of human papillomavirus (HPV) in head and neck cancers, oropharyngeal squamous cell carcinoma (OPSCC). Esophageal squamous cell carcinoma is highly prevalent in the so-called “esophageal cancer belt”, including Northern Iran, Central Asia, North-Central China, along the Rift Valley in East Africa, and South Africa [5]. Among these countries, China is the most affected, in rural areas such as the Henan province [5].
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