INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression.
INAVA promotes aggressiveness of papillary thyroid cancer by upregulating MMP9 expression.
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INAVA 通过上调 MMP9 表达促进甲状腺乳头状癌的侵袭性
DOI：
10.1186/s13578-018-0224-4
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发表时间：
2018
影响因子：
7.5
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Guan H;Guo Y;Liu L;Ye R;Liang W;Li H;Xiao H;Li Y
背景先天免疫激活剂（INAVA）已被证明在肺腺癌中升高。然而，其在甲状腺乳头状癌（PTC）中的表达模式和功能尚不清楚。本研究旨在确定INAVA对PTC的临床，生物学和机制的影响。方法使用癌症基因组图谱数据集，真实的时间PCR和免疫组化，INAVA在PTC中的表达进行了分析。进行功能获得和丧失测定以研究INAVA在PTC细胞侵袭、迁移和转移中的作用。我们采用转录组重测序、真实的时间PCR、蛋白质印迹和免疫组化等方法探讨了INAVA在PTC细胞中作用的分子机制。功能丧失和获得实验表明，INAVA促进PTC细胞在体外和体内的侵袭表型。机制研究表明，INAVA的上调导致成纤维细胞生长因子1（FGF1）的升高，进而增加基质金属蛋白酶9（MMP 9）的表达水平。我们进一步确定，INAVA的水平与临床PTC samples.ConclusionThese数据建立了一个新的作用，INAVA在促进PTC进展，并建议INAVA可能代表一个治疗目标的疾病的FGF 1和MMP 9水平呈正相关。
BackgroundInnate 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.MethodsUsing 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.ResultsWe 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.ConclusionThese data establish a novel role for INAVA in promoting PTC progression and suggest that INAVA may represent a therapeutic target for the disease.
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影响因子：
3.8
作者：
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通讯作者：
Kim, Min Joo
影响因子：
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影响因子：
8.8
作者：
Huang Z;Tan Y;Gu J;Liu Y;Song L;Niu J;Zhao L;Srinivasan L;Lin Q;Deng J;Li Y;Conklin DJ;Neubert TA;Cai L;Li X;Mohammadi M
通讯作者：
Mohammadi M
影响因子：
7.5
作者：
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通讯作者：
Condeelis, John