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CDCA7 通过 TLR4/NF-κB 信号通路调控胃腺癌中的炎症机制。

CDCA7-regulated inflammatory mechanism through TLR4/NF-κB signaling pathway in stomach adenocarcinoma.

机构信息

Department of Pathology, The First People's Hospital of Yibin, Chongqing Medical University, Yibin, China.

出版信息

Biofactors. 2021 Sep;47(5):865-878. doi: 10.1002/biof.1773. Epub 2021 Aug 2.

DOI:10.1002/biof.1773
PMID:34339079
Abstract

To investigate the role of cell division cycle associated 7 (CDCA7) in stomach carcinoma, detect whether CDCA7 knockdown could regulate the development of stomach carcinoma, and further observe the relationship between CDCA7 and inflammation through TLR4/NF-κB signaling pathway in stomach adenocarcinoma (STAD) in vitro and in vivo. TIMER2.0, Kaplan-Meier plotter, Target Gene, and GEPIA systems were used to predict the potential function of CDCA7. Western blot and immunohistochemistry was used to analyze the expression of CDCA7 at different tissue or cell lines. The proliferation, development, inflammation, and apoptosis of STAD in vitro and in vivo were observed by using CDCA7 knockdown lentivirus through TLR4 suppression by its inhibitor. Bioinformatics analysis of CDCA7 with inflammation and western blot of CDCA7 with target protein of immune-associated cells were observed by using CDCA7 knockdown lentivirus in vivo. Finally, the prognosis and associated of CDCA7 in some gene mutations of STAD was observed by Target Gene system. CDCA7 expression in STAD tumor tissue was higher than the normal. The CDCA7 expression in tumor or MGC803 cells was increased. Furthermore, CDCA7 knockdown lentivirus could inhibit STAD development in vitro and in vivo through weakening tumor cells proliferation, reducing tumor volume and biomarker levels, and then increasing apoptotic level. CDCA7 is possibly able to regulate inflammation in STAD through TLR4/NF-κB signaling pathway. Furthermore, CDCA7 may be related with mast cells and the upstream target factor of TLR4/NF-κB signaling pathway in inflammation. These results may provide a new strategy to stomach carcinoma development by regulating inflammation.

摘要

为了研究细胞分裂周期相关蛋白 7(CDCA7)在胃癌中的作用,检测 CDCA7 敲低是否能调控胃癌的发展,并通过体外和体内的 TLR4/NF-κB 信号通路进一步观察 CDCA7 与胃癌(STAD)炎症之间的关系。使用 TIMER2.0、Kaplan-Meier plotter、Target Gene 和 GEPIA 系统预测 CDCA7 的潜在功能。Western blot 和免疫组化分析不同组织或细胞系中 CDCA7 的表达。通过 TLR4 抑制剂抑制 TLR4,使用 CDCA7 敲低慢病毒观察 STAD 在体外和体内的增殖、发展、炎症和凋亡。使用 CDCA7 敲低慢病毒进行体内生物信息学分析和免疫相关细胞的靶蛋白 CDCA7 的 Western blot。最后,通过 Target Gene 系统观察 STAD 中某些基因突变与 CDCA7 的预后和关联。CDCA7 在 STAD 肿瘤组织中的表达高于正常组织。肿瘤或 MGC803 细胞中的 CDCA7 表达增加。此外,CDCA7 敲低慢病毒可通过减弱肿瘤细胞增殖、降低肿瘤体积和生物标志物水平,从而增加凋亡水平,抑制 STAD 在体外和体内的发展。CDCA7 可能通过 TLR4/NF-κB 信号通路调节 STAD 中的炎症。此外,CDCA7 可能与炎症中 TLR4/NF-κB 信号通路的肥大细胞和上游靶因子有关。这些结果可能为通过调节炎症来抑制胃癌发展提供新的策略。

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