HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis

Autor(es)

Morale, Mirian Galliote ^{[1, 2]} ; Abjaude, Walason da Silva ^[3] ; Silva, Aline Montenegro ^[3] ; Villa, Luisa Lina ^{[4, 2]} ; Boccardo, Enrique ^[3]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

^[2] ICESP, Ctr Translat Oncol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Dept Radiol & Oncol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 8, FEB 22 2018.
• Citações Web of Science: 4

Resumo

Cervical cancer is one of the leading causes of cancer death in women worldwide. Persistent infection with high-risk human papillomavirus (HPV) types is the main risk factor for the development of cervical cancer precursor lesions. HPV persistence and tumor development is usually characterized by innate immune system evasion. Alterations in Toll-like receptors (TLR) expression and activation may be important for the control of HPV infections and could play a role in the progression of lesions and tumors. In the present study, we analyzed the mRNA expression of 84 genes involved in TLR signaling pathways. We observed that 80% of the differentially expressed genes were downregulated in cervical cancer cell lines relative to normal keratinocytes. Major alterations were detected in genes coding for several proteins of the TLR signaling axis, including TLR adaptor molecules and genes associated with MAPK pathway, NF kappa B activation and antiviral immune response. In particular, we observed major alterations in the HMGB1-TLR4 signaling axis. Functional analysis also showed that HMGB1 expression is important for the proliferative and tumorigenic potential of cervical cancer cell lines. Taken together, these data indicate that alterations in TLR signaling pathways may play a role in the oncogenic potential of cells expressing HPV oncogenes. (AU)

• Processo FAPESP: 14/21361-4 - Efeito das oncoproteínas de HPV16 nas vias de reparo de dano ao DNA em culturas organotípicas de queratinócitos humanos
• Beneficiário: Aline Montenegro Silva
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• 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: 11/14416-9 - Estudo dos Efeitos de E6 e E7 de HPV16 e HPV6 nas vias de sinalização iniciadas por Toll like receptors (TLR)
• Beneficiário: Mirian Galliote Morale
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 08/57889-1 - Instituto de Ciência e Tecnologia para o Estudo das Doenças Associadas ao Papilomavírus
• Beneficiário: Luisa Lina Villa
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/03232-1 - HPV e microambiente tumoral
• Beneficiário: Luisa Lina Villa
• Modalidade de apoio: Auxílio à Pesquisa - Temático