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Interaction between Cigarette Smoke and Human Papillomavirus 16 E6/E7 Oncoproteins to Induce SOD2 Expression and DNA Damage in Head and Neck Cancer

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Carrillo-Beltran, Diego ; Osorio, Julio C. ; Blanco, Rances ; Oliva, Carolina ; Boccardo, Enrique ; Aguayo, Francisco
Número total de Autores: 6
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 24, n. 8, p. 17-pg., 2023-04-01.

Even though epidemiological studies suggest that tobacco smoking and high-risk human papillomavirus (HR-HPV) infection are mutually exclusive risk factors for developing head and neck cancer (HNC), a portion of subjects who develop this heterogeneous group of cancers are both HPV-positive and smokers. Both carcinogenic factors are associated with increased oxidative stress (OS) and DNA damage. It has been suggested that superoxide dismutase 2 (SOD2) can be independently regulated by cigarette smoke and HPV, increasing adaptation to OS and tumor progression. In this study, we analyzed SOD2 levels and DNA damage in oral cells ectopically expressing HPV16 E6/E7 oncoproteins and exposed to cigarette smoke condensate (CSC). Additionally, we analyzed SOD2 transcripts in The Cancer Genome Atlas (TCGA) Head and Neck Cancer Database. We found that oral cells expressing HPV16 E6/E7 oncoproteins exposed to CSC synergistically increased SOD2 levels and DNA damage. Additionally, the SOD2 regulation by E6, occurs in an Akt1 and ATM-independent manner. This study suggests that HPV and cigarette smoke interaction in HNC promotes SOD2 alterations, leading to increased DNA damage and, in turn, contributing to development of a different clinical entity. (AU)

Processo FAPESP: 10/20002-0 - Estudo de Letalidade Sintética em células infectadas por papilomavírus humano (HPV)
Beneficiário:Enrique Mario Boccardo Pierulivo
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
Processo FAPESP: 19/26065-8 - Regulação da expressão e atividade do inibidor de metaloproteinases de matriz RECK por proteínas precoces de papilomavírus humano: impacto no processo de desenvolvimento tumoral
Beneficiário:Enrique Mario Boccardo Pierulivo
Modalidade de apoio: Auxílio à Pesquisa - Regular