NLRC5 通过激活子宫内膜癌细胞中的 PI3K/AKT 信号通路促进细胞迁移和侵袭。
NLRC5 promotes cell migration and invasion by activating the PI3K/AKT signaling pathway in endometrial cancer.
机构信息
Department of Gynecology and Obstetrics, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
出版信息
J Int Med Res. 2020 May;48(5):300060520925352. doi: 10.1177/0300060520925352.
OBJECTIVE
NOD-like receptor family caspase recruitment domain family domain-containing 5 (NLRC5) is involved in the development of cancer. Our objective was to explore the role of NLRC5 in the progression of endometrial cancer (EC).
METHODS
The roles of NLRC5 in migration and invasion of AN3CA EC cells were examined by cell wound-healing assay, Transwell migration, and invasion analysis. Overexpression of NLRC5 was achieved with NLRC5 plasmid, and knockdown of NLRC5 was achieved using small interfering (si)RNA-NLRC5 in AN3CA cells. The expression of NLRC5 was detected by immunohistochemical, western blot, and quantitative real-time PCR. LY294002 was used to inhibit the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway.
RESULTS
NLRC5 was downregulated in EC tissue compared with normal endometrium. Overexpression of NLRC5 led to upregulation of cell migration and invasion in AN3CA cells and expression of matrix metallopeptidase (MMP)-9. Inhibition of NLRC5 restricted migration and invasion of AN3CA cells and expression of MMP9. Overexpression of NLRC5 promoted the activation of PI3K/AKT signaling pathway. Inhibiting PI3K/AKT signaling pathway by using LY294002 blocked the positive role of NLRC5 in migration and invasion of AN3CA cells and expression of MMP9.
CONCLUSIONS
These results demonstrate that NLRC5 promotes EC progression by activating the PI3K/AKT signaling pathway.
目的
核苷酸结合寡聚化结构域样受体家族含 caspase 募集结构域家族蛋白 5（NLRC5）参与癌症的发生发展。本研究旨在探讨 NLRC5 在子宫内膜癌（EC）进展中的作用。
方法
通过细胞划痕实验、Transwell 迁移和侵袭分析检测 NLRC5 在 AN3CA 子宫内膜癌细胞迁移和侵袭中的作用。通过 NLRC5 质粒过表达 NLRC5，通过 siRNA-NLRC5 敲低 AN3CA 细胞中的 NLRC5。通过免疫组织化学、Western blot 和实时定量 PCR 检测 NLRC5 的表达。使用 LY294002 抑制磷脂酰肌醇 3-激酶（PI3K）/AKT 信号通路。
结果
与正常子宫内膜相比，EC 组织中 NLRC5 表达下调。NLRC5 过表达导致 AN3CA 细胞迁移和侵袭增加，基质金属蛋白酶（MMP）-9 表达上调。抑制 NLRC5 限制了 AN3CA 细胞的迁移和侵袭以及 MMP9 的表达。NLRC5 过表达促进了 PI3K/AKT 信号通路的激活。使用 LY294002 抑制 PI3K/AKT 信号通路阻断了 NLRC5 对 AN3CA 细胞迁移和侵袭以及 MMP9 表达的正向作用。
结论
这些结果表明，NLRC5 通过激活 PI3K/AKT 信号通路促进 EC 的进展。
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