HPV 16 E6 promotes growth and metastasis of esophageal squamous cell carcinoma cells in vitro

Mol Biol Rep. 2023 Feb;50(2):1181-1190. doi: 10.1007/s11033-022-07952-7. Epub 2022 Nov 26.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide. Increasing evidence suggests that human papillomavirus (HPV) infection may be associated with the etiology of ESCC. However, the precise role of HPV in ESCC remains unclear.

Methods and results: Proliferation and apoptosis of ESCC cells upon infection with HPV16 E6 were detected using CCK-8 assays and Western blot analyses. The migration rate was measured with a wound healing assay, and a Transwell Matrigel invasion assay was used to detect the invasive ability. RT-qPCR was performed to detect the expression of E6AP, p53, and miR-34a. The proliferation rates were significantly higher in HPV16E6-transfected cell groups compared with the negative control groups. Bax protein expression was downregulated in HPV16E6-treated groups compared to the controls. The wound healing and Transwell Matrigel invasion assays indicated that HPV16 E6 infection could increase ESCC cell migration and invasion. Furthermore, E6AP, p53 and miR-34a expression were decreased in HPV16 E6-transfected cell lines.

Conclusion: Our results not only provide evidence that HPV16 E6 promotes cell proliferation, migration, and invasion in ESCC, but also suggests a correlation between HPV infection and E6AP, p53 and miR-34a expression. Consequently, HPV16 E6 may play an important role in ESCC development.

Keywords: Apoptosis; Esophageal squamous cell carcinoma; Human papillomavirus; Invasion; Migration; Proliferation.

MeSH terms

  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Squamous Cell Carcinoma* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / metabolism
  • Humans
  • MicroRNAs* / genetics
  • Neoplasm Invasiveness
  • Papillomavirus Infections* / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Tumor Suppressor Protein p53
  • MicroRNAs