The Novel Protein ADAMTS16 Promotes Gastric Carcinogenesis by Targeting IFI27 through the NF-κb Signaling Pathway.
The Novel Protein ADAMTS16 Promotes Gastric Carcinogenesis by Targeting IFI27 through the NF-κb Signaling Pathway.
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新型蛋白质 ADAMTS16 通过 NF-κb 信号通路靶向 IFI27 促进胃癌发生
DOI：
10.3390/ijms231911022
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发表时间：
2022-09-20
影响因子：
5.6
通讯作者：
Yang, Zuli
中科院分区：
文献类型：
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作者：
Li, Tuoyang;Zhou, Junyi;Jiang, Yingming;Zhao, Yandong;Huang, Jintuan;Li, Weiyao;Huang, Zhenze;Chen, Zijian;Tang, Xiaocheng;Chen, Hao;Yang, Zuli
具有血小板反应蛋白基序的去整合素和金属蛋白酶16（ADAMTS 16）已被报道参与实体癌的发病机制。然而，其在胃癌（GC）中的作用尚不清楚。本研究探讨ADAMTS 16在胃癌中的作用。通过体内和体外功能实验研究ADAMTS 16对细胞迁移、侵袭和增殖的影响。通过生物信息学分析、免疫共沉淀和免疫荧光等方法对ADAMTS 16的下游信号通路进行了确认。同时，采用生物信息学分析、qRT-PCR、western blot和双荧光素酶报告基因分析等方法对ADAMTS 16靶基因进行鉴定。在公开数据集中分析ADAMTS 16在GC中的表达。采用免疫组化方法检测胃癌组织中ADAMTS 16的表达及其与胃癌临床特征的关系。异位ADAMTS 16表达显著促进肿瘤细胞迁移、侵袭和生长。生物信息学分析和western blot结果表明，ADAMTS 16通过NF-κB途径上调IFI 27蛋白表达，免疫荧光和western blot结果证实了这一点。双荧光素酶报告基因分析鉴定了P65和IFI 27之间的结合位点，其可能直接参与IFI 27的转录调控。IFI 27敲低逆转了ADAMTS 16对细胞侵袭、迁移和增殖的促进作用，表明ADAMTS 16通过靶向NF-κB/IFI 27轴作用于GC细胞。ADAMTS 16在临床特征中与预后不良相关。ADAMTS 16通过NF-κB通路靶向IFI 27促进细胞迁移、侵袭和增殖，是GC潜在的进展和存活生物标志物。
A disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16) has been reported to be involved in the pathogenesis of solid cancers. However, its role in gastric cancer (GC) is unclear. In this study, the role of ADAMTS16 in gastric cancer was investigated. The effects of ADAMTS16 on cell migration, invasion, and proliferation were investigated by functional experiments in vivo and in vitro. Downstream signal pathways of ADAMTS16 were confirmed by using bioinformatics analysis, co-immunoprecipitation, and immunofluorescence. Meanwhile, bioinformatics analysis, qRT-PCR, western blot, and dual-luciferase reporter gene analysis assays were used to identify ADAMTS16 targets. The expression of ADAMTS16 in GC was analyzed in public datasets. The expression of ADAMTS16 and its correlations with the clinical characteristics of GC were investigated by immunohistochemistry. Ectopic ADAMTS16 expression significantly promoted tumor cell migration, invasion, and growth. Bioinformatics analysis and western blot showed that ADAMTS16 upregulated the IFI27 protein through the NF-κb pathway, which was confirmed by immunofluorescence and western blot. Dual-luciferase reporter gene analysis identified a binding site between P65 and IFI27 that may be directly involved in the transcriptional regulation of IFI27. IFI27 knockdown reversed the promoting effect of ADAMTS16 on cell invasion, migration, and proliferation indicating that ADAMTS16 acts on GC cells by targeting the NF-κb/IFI27 axis. ADAMTS16 was associated with poor prognosis in clinical characteristics. ADAMTS16 promotes cell migration, invasion, and proliferation by targeting IFI27 through the NF-κB pathway and is a potential progressive and survival biomarker of GC.
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DOI：
10.1016/j.matbio.2018.06.002
发表时间：
2018-10
期刊：
Matrix biology : journal of the International Society for Matrix Biology
影响因子：
--
作者：
Mead TJ;Apte SS
通讯作者：
Apte SS
ADAMTS-6 是食管鳞状细胞癌患者预后不良的预测因子
影响因子：
3.6
作者：
Liu, Lan;Yang, Zhaoting;Xuan, Yanhua
通讯作者：
Xuan, Yanhua
影响因子：
29.4
作者：
Jun, Jae Kwan;Choi, Kui Son;Lee, Dukhyoung
通讯作者：
Lee, Dukhyoung
影响因子：
12.3
作者：
Kelwick R;Desanlis I;Wheeler GN;Edwards DR
通讯作者：
Edwards DR
影响因子：
2.9
作者：
通讯作者：
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