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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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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. |
format | Online Article Text |
id | pubmed-5887255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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