INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression

Hongyu Guan, Yan Guo, Liehua Liu, Runyi Ye, Weiwei Liang, Hai Li, Haipeng Xiao, Yanbing Li

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. 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. 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. These data establish a novel role for INAVA in promoting PTC progression and suggest that INAVA may represent a therapeutic target for the disease.