DNA demethylation agent 5azadC downregulates HPV16 E6 expression in cervical cancer cell lines independently of TBX2 expression

HPV16 is the most carcinogenic human papillomavirus and causes >50% of cervical cancers, the majority of anal cancers and 30% of oropharyngeal squamous cell carcinomas. HPV carcinogenesis relies on the continuous expression of the two main viral oncoproteins E6 and E7 that target >150 cellular proteins. Among them, epigenetic modifiers, including DNA Methyl Transferases (DNMT), are dysregulated, promoting an aberrant methylation pattern in HPV-positive cancer cells. It has been previously reported that the treatment of HPV-positive cervical cancer cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5azadC) caused the downregulation of E6 expression due to mRNA destabilization that was mediated by miR-375. Recently, the T-box transcription factor 2 (TBX2) has been demonstrated to repress HPV LCR activity. In the current study, the role of TBX2 in E6 repression was investigated in HPV16 cervical cancer cell lines following 5azadC treatment. A decrease of E6 expression was accompanied by p53 and p21 restoration. While TBX2 mRNA was upregulated in 5azadC-treated SiHa and Ca Ski cells, TBX2 protein was not detectable. Furthermore, the overexpression of TBX2 protein in cervical cancer cells did not allow the repression of E6 expression. The TBX2 transcription factor is therefore unlikely to be associated with the repression of E6 following 5azadC treatment of SiHa and Ca Ski cells. © 2020 Spandidos Publications. All rights reserved.

• Fecha de publicación: 2020
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/22720
• Acceso en línea: https://doi.org/10.3892/ol.2019.11158; https://repository.urosario.edu.co/handle/10336/22720
• Palabra clave: Decitabine; Methyltransferase; Microrna 375; Protein e6; Protein e7; Protein p21; Protein p53; Small interfering rna; T box transcription factor; Article; Ca ski cell line; Carcinogenesis; Cervical cancer cell line; Chemoluminescence; Controlled study; Dna demethylation; Down regulation; Gene overexpression; Gene repression; Genetic transfection; Hela cell line; Human; Human cell; Human papillomavirus 16 infection; Human papillomavirus type 16; Immune dysregulation; Immunoblotting; Immunoprecipitation; Luciferase assay; Mcf-7 cell line; Mrna expression level; Papillomavirus infection; Protein expression; Protein expression level; Reverse transcription polymerase chain reaction; Rna extraction; Siha cell line; Upregulation; Uterine cervix cancer; Western blotting; 5-aza-2'-deoxycytidine; Dna methyltransferase inhibitor; Epigenetic; Human papillomavirus-induced cancer; T-box
• License: Abierto (Texto Completo)