| Autor: |
Rosendo-Chalma P; Programa de Doctorado en Ciencias Biomédicas, Instituto de Investigaciones Biomédicas (IIB), Universidad Nacional Autónoma de México (UNAM), Mexico City 10450, Mexico., Antonio-Vejar V; Laboratorio de Virus y Cáncer, Unidad de Investigación Biomédica en Cáncer of Instituto de Investigaciones Biomédicas‑Universidad Nacional Autónoma de México (IIB‑UNAM) and División de Investigación Básica of Instituto Nacional de Cancerología‑Secretaría de Salud (INCan‑SSA), Mexico City 14080, Mexico., Bigoni-Ordóñez GD; Laboratorio de Virus y Cáncer, Unidad de Investigación Biomédica en Cáncer of Instituto de Investigaciones Biomédicas‑Universidad Nacional Autónoma de México (IIB‑UNAM) and División de Investigación Básica of Instituto Nacional de Cancerología‑Secretaría de Salud (INCan‑SSA), Mexico City 14080, Mexico., Patiño-Morales CC; Laboratorio de Virus y Cáncer, Unidad de Investigación Biomédica en Cáncer of Instituto de Investigaciones Biomédicas‑Universidad Nacional Autónoma de México (IIB‑UNAM) and División de Investigación Básica of Instituto Nacional de Cancerología‑Secretaría de Salud (INCan‑SSA), Mexico City 14080, Mexico., Cano-García A; Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC‑UAM), Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), Madrid 28029, Spain., García-Carrancá A; Laboratorio de Virus y Cáncer, Unidad de Investigación Biomédica en Cáncer of Instituto de Investigaciones Biomédicas‑Universidad Nacional Autónoma de México (IIB‑UNAM) and División de Investigación Básica of Instituto Nacional de Cancerología‑Secretaría de Salud (INCan‑SSA), Mexico City 14080, Mexico. |
| Abstrakt: |
A common characteristic of cancer types associated with viruses is the dysregulated expression of the CDH1 gene, which encodes E‑cadherin, in general by activation of DNA methyltransferases (Dnmts). In cervical cancer, E7 protein from high risk human papillomaviruses (HPVs) has been demonstrated to interact with Dnmt1 and histone deacetylase type 1 (HDAC1). The present study proposed that E7 may regulate the expression of CDH1 through two pathways: i) Epigenetic, including DNA methylation; and ii) Epigenetic‑independent, including the induction of negative regulators of CDH1 expression, such as Snail family transcriptional repressor Snai1 and Snai2. To test this hypothesis, HPV16‑ and HPV18‑positive cell lines were used to determine the methylation pattern of the CDH1 promoter and its expression in association with its negative regulators. Different methylation frequencies were identified in the CDH1 promoter in HeLa (88.24%) compared with SiHa (17.65%) and Ca Ski (0%) cell lines. Significant differences in the expression of SNAI1 were observed between these cell lines, and an inverse association was identified between the expression levels of SNAI1 and CDH1. In addition, suppressing E7 not only increased the expression of CDH1, but notably decreased the expression of SNAI1 and modified the methylation pattern of the CDH1 promoter. These results suggested that the expression of CDH1 was dependent on the expression of SNAI1 and was inversely associated with the expression of E7. The present results indicated that E7 from HPV16/18 regulated the expression of CDH1 by the two following pathways in which Snai1 is involved: i) Hypermethylation of the CDH1 promoter region and increasing expression of SNAI1, as observed in HeLa; and ii) Hypomethylation of the CDH1 promoter region and expression of SNAI1, as observed in SiHa. Therefore, the suppression of CDH1 and expression of SNAI1 may be considered to be biomarkers of metastasis in uterine cervical cancer. |
