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INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression

BACKGROUND: Innate immunity activator (INAVA) has been shown to be elevated in lung adenocarcinoma. However, its expression pattern and function in papillary thyroid cancer (PTC) are unknown. This study aimed to identify the clinical, biological, and mechanistic impacts of INAVA on PTC. METHODS: Usi...

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Autores principales: Guan, Hongyu, Guo, Yan, Liu, Liehua, Ye, Runyi, Liang, Weiwei, Li, Hai, Xiao, Haipeng, Li, Yanbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887255/
https://www.ncbi.nlm.nih.gov/pubmed/29632659
http://dx.doi.org/10.1186/s13578-018-0224-4
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author Guan, Hongyu
Guo, Yan
Liu, Liehua
Ye, Runyi
Liang, Weiwei
Li, Hai
Xiao, Haipeng
Li, Yanbing
author_facet Guan, Hongyu
Guo, Yan
Liu, Liehua
Ye, Runyi
Liang, Weiwei
Li, Hai
Xiao, Haipeng
Li, Yanbing
author_sort Guan, Hongyu
collection PubMed
description BACKGROUND: Innate immunity activator (INAVA) has been shown to be elevated in lung adenocarcinoma. However, its expression pattern and function in papillary thyroid cancer (PTC) are unknown. This study aimed to identify the clinical, biological, and mechanistic impacts of INAVA on PTC. METHODS: Using The Cancer Genome Atlas dataset, real time PCR, and immunohistochemistry, the expression of INAVA in PTC was analyzed. Gain- and loss-of-function assays were performed to investigate the role of INAVA in PTC cell invasion, migration, and metastasis. We explored the molecular mechanisms underlying the roles of INAVA in PTC cells using transcriptome resequencing, real time PCR, western blotting and immunohistochemistry. RESULTS: We found that INAVA expression was significantly upregulated in PTC and was significantly associated with lymph node metastasis. Loss- and gain-of-function experiments demonstrated that INAVA promoted the aggressive phenotype of PTC cells in vitro and in vivo. Mechanistic study suggested that upregulation of INAVA resulted in elevated fibroblast growth factor 1 (FGF1), which in turn increased the expression level of matrix metalloproteinases 9 (MMP9). We further identified that the level of INAVA was positively correlated with the levels of FGF1 and MMP9 in clinical PTC specimens. CONCLUSION: These data establish a novel role for INAVA in promoting PTC progression and suggest that INAVA may represent a therapeutic target for the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13578-018-0224-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-58872552018-04-09 INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression Guan, Hongyu Guo, Yan Liu, Liehua Ye, Runyi Liang, Weiwei Li, Hai Xiao, Haipeng Li, Yanbing Cell Biosci Research BACKGROUND: Innate immunity activator (INAVA) has been shown to be elevated in lung adenocarcinoma. However, its expression pattern and function in papillary thyroid cancer (PTC) are unknown. This study aimed to identify the clinical, biological, and mechanistic impacts of INAVA on PTC. METHODS: Using The Cancer Genome Atlas dataset, real time PCR, and immunohistochemistry, the expression of INAVA in PTC was analyzed. Gain- and loss-of-function assays were performed to investigate the role of INAVA in PTC cell invasion, migration, and metastasis. We explored the molecular mechanisms underlying the roles of INAVA in PTC cells using transcriptome resequencing, real time PCR, western blotting and immunohistochemistry. RESULTS: We found that INAVA expression was significantly upregulated in PTC and was significantly associated with lymph node metastasis. Loss- and gain-of-function experiments demonstrated that INAVA promoted the aggressive phenotype of PTC cells in vitro and in vivo. Mechanistic study suggested that upregulation of INAVA resulted in elevated fibroblast growth factor 1 (FGF1), which in turn increased the expression level of matrix metalloproteinases 9 (MMP9). We further identified that the level of INAVA was positively correlated with the levels of FGF1 and MMP9 in clinical PTC specimens. CONCLUSION: These data establish a novel role for INAVA in promoting PTC progression and suggest that INAVA may represent a therapeutic target for the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13578-018-0224-4) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-05 /pmc/articles/PMC5887255/ /pubmed/29632659 http://dx.doi.org/10.1186/s13578-018-0224-4 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Guan, Hongyu
Guo, Yan
Liu, Liehua
Ye, Runyi
Liang, Weiwei
Li, Hai
Xiao, Haipeng
Li, Yanbing
INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression
title INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression
title_full INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression
title_fullStr INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression
title_full_unstemmed INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression
title_short INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression
title_sort inava promotes aggressiveness of papillary thyroid cancer by upregulating mmp9 expression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887255/
https://www.ncbi.nlm.nih.gov/pubmed/29632659
http://dx.doi.org/10.1186/s13578-018-0224-4
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