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SPOCK1通过调节NF-κB通路和诱导上皮-间质转化促进结肠癌细胞的增殖和迁移。

SPOCK1 promotes the proliferation and migration of colon cancer cells by regulating the NF-κB pathway and inducing EMT.

作者信息

Liu Han-Xiong, Cao Yuan-Yuan, Qu Jia-Yao

机构信息

Department of Gastroenterology, The First People's Hospital of Chenzhou, Chenzhou, China.

Department of Critical Care Medicine, The First People's Hospital of Chenzhou, Chenzhou, China.

出版信息

Neoplasma. 2021 Jul;68(4):702-710. doi: 10.4149/neo_2021_201031N1158. Epub 2021 Apr 23.

Abstract

Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) has been shown to promote various tumors, but its role in colon cancer (CRC) has not been clearly illuminated. The aim of this study was to investigate the effects of SPOCK1 interference on the proliferation, migration, and EMT of CRC cells. First, we analyzed the expression of SPOCK1 in various CRC datasets. Then, we investigated the correlation between SPOCK1 and prognosis in CRC patients. We overexpressed SPOCK1 and knocked down SPOCK1 expression in HCT-116 and SW480 cells, respectively. Then, cell proliferation was assayed with a CCK-8 assay, and cell migration was evaluated with a Transwell migration assay. NF-κB and EMT-related proteins were studied by western blotting. The results indicated that the mRNA levels of SPOCK1 were relatively high in CRC tissues and that high expression of SPOCK1 was negatively correlated with patient prognosis. With SPOCK1 overexpression in HCT-116 cells, cell proliferation and migration were increased, while SPOCK1 knockdown had the opposite effects. With SPOCK1 overexpression in HCT-116 cells, the expression levels of NF-κB and EMT-related proteins were elevated, while SPOCK1 knockdown produced the opposite results. In conclusion, our study demonstrates that SPOCK1 may activate the NF-κB/Snail signaling cascade to promote the proliferation and migration of CRC cells. SPOCK1 may serve as a new prognostic indicator and potential therapeutic target in CRC.

摘要

富含半胱氨酸的酸性分泌蛋白/骨连接蛋白、富含半胱氨酸/色氨酸/半胱氨酸/缬氨酸基序和Kazal样结构域蛋白聚糖1(SPOCK1)已被证明可促进多种肿瘤的发生发展,但其在结肠癌(CRC)中的作用尚未明确阐明。本研究旨在探讨SPOCK1干扰对CRC细胞增殖、迁移和上皮-间质转化(EMT)的影响。首先,我们分析了SPOCK1在各种CRC数据集里的表达情况。然后,我们研究了SPOCK1与CRC患者预后之间的相关性。我们分别在HCT-116和SW480细胞中过表达SPOCK1并敲低SPOCK1的表达。然后,用CCK-8法检测细胞增殖情况,并用Transwell迁移实验评估细胞迁移能力。通过蛋白质印迹法研究核因子κB(NF-κB)和EMT相关蛋白。结果表明,SPOCK1的mRNA水平在CRC组织中相对较高,且SPOCK1的高表达与患者预后呈负相关。在HCT-116细胞中过表达SPOCK1时,细胞增殖和迁移增加,而敲低SPOCK1则产生相反的效果。在HCT-116细胞中过表达SPOCK1时,NF-κB和EMT相关蛋白的表达水平升高,而敲低SPOCK1则产生相反的结果。总之,我们的研究表明,SPOCK1可能激活NF-κB/蜗牛(Snail)信号级联反应,以促进CRC细胞的增殖和迁移。SPOCK1可能作为CRC的一种新的预后指标和潜在的治疗靶点。

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