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Transcriptional Suppression of E-Cadherin by Hpv-16 E6 and E7 Oncogenes Is Independent of Hypermethylation of E-Cadherin Promoter Publisher



Faghihloo E1 ; Sadeghizadeh M2 ; Shahmahmoodi S1 ; Mokhtariazad T1
Authors
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Authors Affiliations
  1. 1. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Source: Iranian Red Crescent Medical Journal Published:2017


Abstract

Background: Cervical cancer is one of the most common cancers observed in women worldwide, and its development is related to E6 and E7 two viral oncoproteins of high-risk human papillomavirus (HPV) types. Aberrant expression of E-cadherin, which is associated with epithelial-to-mesenchymal transition (EMT), is frequently observed in cervical cancer. Objectives: The mechanisms underlying E-cadherin suppression in cervical cancer are not clear; therefore, this experimental study from Iran was designed to elucidate the relationship of DNA methyltransferase expression and E-cadherin promoter methylation with E-cadherin expression in HPV-16 E6- and E7-expressing cells. Materials and Methods: Real-time PCR and western blot were used to determine the effects of HPV-16 E6 and E7 on E-cadherin, DNMT1, DNMT3a, and DNMT3b expression in HCT-116 cell line. We also analyzed E-cadherin promoter methylation in cells expressing HPV-16 E6 and E7 oncoproteins by bisulfite sequencing. Results: HPV-16 E6 and E7 proteins reduced E-cadherin expression 3.7 and 2.2 times when compared with control cells (P = 0.0221 and P = 0.0461, respectively). This reduction was greater in HPV-16 E6-expressing cells than in HPV-16 E7-expressing cells. Although HPV-16 E6 and E7 increased DNA methyltransferase 1 expression 2.6 and 3.4 times, respectively (P = 0.0133 and P = 0.0113) when compared with control cells, they was no E-cadherin promoter methylation. Conclusions: Unlike other cancer-associated viruses (HBV, HCV, and EBV), reduction in E-cadherin expression in HPV-16 E6- and E7-expressing cells is not due to hypermethylation of the E-cadherin promoter. © 2016, Iranian Red Crescent Medical Journal.