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

Abstract 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 characteri...

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Autores principales:	Mirian Galliote Morale, Walason da Silva Abjaude, Aline Montenegro Silva, Luisa Lina Villa, Enrique Boccardo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e29ee4ccaa644ff1bfb12c75138de0f1
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spelling	oai:doaj.org-article:e29ee4ccaa644ff1bfb12c75138de0f12021-12-02T11:40:16ZHPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis10.1038/s41598-018-21416-82045-2322https://doaj.org/article/e29ee4ccaa644ff1bfb12c75138de0f12018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21416-8https://doaj.org/toc/2045-2322Abstract 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, NFκB 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.Mirian Galliote MoraleWalason da Silva AbjaudeAline Montenegro SilvaLuisa Lina VillaEnrique BoccardoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mirian Galliote Morale Walason da Silva Abjaude Aline Montenegro Silva Luisa Lina Villa Enrique Boccardo HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis
description	Abstract 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, NFκB 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.
format	article
author	Mirian Galliote Morale Walason da Silva Abjaude Aline Montenegro Silva Luisa Lina Villa Enrique Boccardo
author_facet	Mirian Galliote Morale Walason da Silva Abjaude Aline Montenegro Silva Luisa Lina Villa Enrique Boccardo
author_sort	Mirian Galliote Morale
title	HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis
title_short	HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis
title_full	HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis
title_fullStr	HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis
title_full_unstemmed	HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis
title_sort	hpv-transformed cells exhibit altered hmgb1-tlr4/myd88-sarm1 signaling axis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/e29ee4ccaa644ff1bfb12c75138de0f1
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HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis

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