INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression

Cell & Bioscience

Haipeng Xiao¹  Yanbing Li¹  Weiwei Liang¹  Hongyu Guan¹  Yan Guo¹  Liehua Liu¹  Hai Li¹  Runyi Ye² 

[1] Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University;Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Sun Yat-sen University;

关键词: INAVA;    Papillary thyroid cancer;    Invasion;    MMP9;    FGF1;   

DOI  :  10.1186/s13578-018-0224-4

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown