Obstetrics and Gynecology Department, The First Affiliated Hospital of JinZhou Medical University, No. 2, Section 5, Renmin Street, JinZhou City, 121000, LiaoNing Province, China.
Histochem Cell Biol. 2022 Feb;157(2):173-182. doi: 10.1007/s00418-021-02055-z. Epub 2021 Nov 26.
The goal of this study was to investigate the role and mechanism of action of nucleotide oligomerization domain receptor 1 (NOD1) in ovarian cancer. Results showed that the expressions of NOD1 and receptor interacting serine/threonine kinase 2 (RIPK2) were notably upregulated in non-metastatic and metastatic ovarian tumors compared with matched non-tumor tissues, and their expression in metastatic tumor tissues was higher than that in non-metastatic tumors. Overexpression of NOD1 facilitated the expression of proliferation-related proteins (PCNA and Ki67) and proliferation and invasion of ovarian cancer cells. Overexpression of NOD1 promoted NF-κB expression and phosphorylation. Importantly, NOD1 bound with RIPK2, and silencing of RIPK2 partly rescued the promotion of NOD1 to NF-κB expression and its phosphorylation. The promotion of NOD1 to ovarian cancer cell proliferation and invasion was partly reversed by RIPK2 silencing. Results from our in vivo study indicate that overexpression of NOD1 accelerated the growth of ovarian cancer tumors, expression of proliferation-related proteins, and activation of NF-κB. However, silencing of NOD1 suppressed tumor growth. In summary, NOD1 facilitates ovarian cancer progression by activating NF-κB signaling by binding to RIPK2. We suggest a new strategy for the treatment of ovarian cancer.
本研究旨在探讨核苷酸寡聚化结构域受体 1（NOD1）在卵巢癌中的作用和机制。结果表明，与匹配的非肿瘤组织相比，非转移性和转移性卵巢肿瘤中 NOD1 和受体相互作用丝氨酸/苏氨酸激酶 2（RIPK2）的表达明显上调，转移性肿瘤组织中的表达高于非转移性肿瘤。NOD1 的过表达促进了增殖相关蛋白（PCNA 和 Ki67）的表达以及卵巢癌细胞的增殖和侵袭。NOD1 的过表达促进了 NF-κB 的表达和磷酸化。重要的是，NOD1 与 RIPK2 结合，沉默 RIPK2 部分挽救了 NOD1 对 NF-κB 表达及其磷酸化的促进作用。沉默 RIPK2 部分逆转了 NOD1 对卵巢癌细胞增殖和侵袭的促进作用。体内研究结果表明，NOD1 的过表达加速了卵巢癌肿瘤的生长、增殖相关蛋白的表达和 NF-κB 的激活。然而，沉默 NOD1 抑制了肿瘤的生长。总之，NOD1 通过与 RIPK2 结合激活 NF-κB 信号通路促进卵巢癌的进展。我们为卵巢癌的治疗提供了一种新的策略。
