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HHV-6A Infection of Papillary Thyroid Cancer Cells Induces Several Effects Related to Cancer Progression

Recent studies have shown that thyrocytes are permissive to HHV-6A infection and that the virus may contribute to the pathogenesis of autoimmune thyroiditis. Thyroid autoimmune diseases increase the risk of papillary cancer, which is not surprising considering that chronic inflammation activates pat...

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Autores principales: Mardente, Stefania, Romeo, Maria Anele, Asquino, Angela, Po, Agnese, Gilardini Montani, Maria Saveria, Cirone, Mara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612057/
https://www.ncbi.nlm.nih.gov/pubmed/37896899
http://dx.doi.org/10.3390/v15102122
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author Mardente, Stefania
Romeo, Maria Anele
Asquino, Angela
Po, Agnese
Gilardini Montani, Maria Saveria
Cirone, Mara
author_facet Mardente, Stefania
Romeo, Maria Anele
Asquino, Angela
Po, Agnese
Gilardini Montani, Maria Saveria
Cirone, Mara
author_sort Mardente, Stefania
collection PubMed
description Recent studies have shown that thyrocytes are permissive to HHV-6A infection and that the virus may contribute to the pathogenesis of autoimmune thyroiditis. Thyroid autoimmune diseases increase the risk of papillary cancer, which is not surprising considering that chronic inflammation activates pathways that are also pro-oncogenic. Moreover, in this condition, cell proliferation is stimulated as an attempt to repair tissue damage caused by the inflammatory process. Interestingly, it has been reported that the well-differentiated papillary thyroid carcinoma (PTC), the less aggressive form of thyroid tumor, may progress to the more aggressive follicular thyroid carcinoma (FTC) and eventually to the anaplastic thyroid carcinoma (ATC), and that to such progression contributes the presence of an inflammatory/immune suppressive tumor microenvironment. In this study, we investigated whether papillary tumor cells (BCPAP) could be infected by human herpes virus-6A (HHV-6A), and if viral infection could induce effects related to cancer progression. We found that the virus dysregulated the expression of several microRNAs, such as miR-155, miR-9, and the miR-221/222 cluster, which are involved in different steps of carcinogenesis, and increased the secretion of pro-inflammatory cytokines, particularly IL-6, which may also sustain thyroid tumor cell growth and promote cancer progression. Genomic instability and the expression of PTEN, reported to act as an oncogene in mutp53-carrying cells such as BCPAP, also increased following HHV-6A-infection. These findings suggest that a ubiquitous herpesvirus such as HHV-6A, which displays a marked tropism for thyrocytes, could be involved in the progression of PTC towards more aggressive forms of thyroid tumor.
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spelling pubmed-106120572023-10-29 HHV-6A Infection of Papillary Thyroid Cancer Cells Induces Several Effects Related to Cancer Progression Mardente, Stefania Romeo, Maria Anele Asquino, Angela Po, Agnese Gilardini Montani, Maria Saveria Cirone, Mara Viruses Article Recent studies have shown that thyrocytes are permissive to HHV-6A infection and that the virus may contribute to the pathogenesis of autoimmune thyroiditis. Thyroid autoimmune diseases increase the risk of papillary cancer, which is not surprising considering that chronic inflammation activates pathways that are also pro-oncogenic. Moreover, in this condition, cell proliferation is stimulated as an attempt to repair tissue damage caused by the inflammatory process. Interestingly, it has been reported that the well-differentiated papillary thyroid carcinoma (PTC), the less aggressive form of thyroid tumor, may progress to the more aggressive follicular thyroid carcinoma (FTC) and eventually to the anaplastic thyroid carcinoma (ATC), and that to such progression contributes the presence of an inflammatory/immune suppressive tumor microenvironment. In this study, we investigated whether papillary tumor cells (BCPAP) could be infected by human herpes virus-6A (HHV-6A), and if viral infection could induce effects related to cancer progression. We found that the virus dysregulated the expression of several microRNAs, such as miR-155, miR-9, and the miR-221/222 cluster, which are involved in different steps of carcinogenesis, and increased the secretion of pro-inflammatory cytokines, particularly IL-6, which may also sustain thyroid tumor cell growth and promote cancer progression. Genomic instability and the expression of PTEN, reported to act as an oncogene in mutp53-carrying cells such as BCPAP, also increased following HHV-6A-infection. These findings suggest that a ubiquitous herpesvirus such as HHV-6A, which displays a marked tropism for thyrocytes, could be involved in the progression of PTC towards more aggressive forms of thyroid tumor. MDPI 2023-10-19 /pmc/articles/PMC10612057/ /pubmed/37896899 http://dx.doi.org/10.3390/v15102122 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mardente, Stefania
Romeo, Maria Anele
Asquino, Angela
Po, Agnese
Gilardini Montani, Maria Saveria
Cirone, Mara
HHV-6A Infection of Papillary Thyroid Cancer Cells Induces Several Effects Related to Cancer Progression
title HHV-6A Infection of Papillary Thyroid Cancer Cells Induces Several Effects Related to Cancer Progression
title_full HHV-6A Infection of Papillary Thyroid Cancer Cells Induces Several Effects Related to Cancer Progression
title_fullStr HHV-6A Infection of Papillary Thyroid Cancer Cells Induces Several Effects Related to Cancer Progression
title_full_unstemmed HHV-6A Infection of Papillary Thyroid Cancer Cells Induces Several Effects Related to Cancer Progression
title_short HHV-6A Infection of Papillary Thyroid Cancer Cells Induces Several Effects Related to Cancer Progression
title_sort hhv-6a infection of papillary thyroid cancer cells induces several effects related to cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612057/
https://www.ncbi.nlm.nih.gov/pubmed/37896899
http://dx.doi.org/10.3390/v15102122
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