Department of Gynecology and Obstetrics, Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Gynecologic Minimally Invasive Surgery Research Center, Tongji University School of Medicine, Shanghai, China.
Cell Death Dis. 2018 Sep 5;9(9):908. doi: 10.1038/s41419-018-0881-6.
Emerging evidence suggests that the members of the tripartite motif (TRIM) family play a crucial role in cancer development and progression. The purpose of the study was to explore TRIM52's role in tumorigenesis and its potential molecular mechanism in ovarian cancer. The study demonstrated that knockdown of TRIM52 in SKOV3 and CAOV3 cells inhibited ovarian cancer cell invasion, migration, and proliferation, and induced cell apoptosis. On the contrary, overexpression of TRIM52 in HO8910 cells showed contrary results. Further, overexpression of TRIM52 enhanced the expression of phosphorylated IKKβ and IKBα proteins and nuclear protein P65, which implied the activation of NF-kB signal pathway. Knockdown of TRIM52 downregulated the mRNA and protein levels of NF-kB signal downstream effectors of the NF-kB pathway, including MMP9, Bcl2, IL8, and TNFα, but upregulated caspase-3 expression. These results suggested that activation of the NF-kB pathway is involved in TRIM52-mediated regulation in ovarian cancer. The nude mice study further confirmed that knockdown of TRIM52 blocked tumor growth, inhibited cell proliferation, and promoted cell apoptosis. Our data strongly suggested that TRIM52 plays an oncogenic role in ovarian cancer development associated with the NF-kB signal pathway and may be a potential target for cancer therapy.
新出现的证据表明，三部分基序 (TRIM) 家族成员在癌症的发生和发展中起着至关重要的作用。本研究旨在探讨 TRIM52 在肿瘤发生中的作用及其在卵巢癌中的潜在分子机制。研究表明，在 SKOV3 和 CAOV3 细胞中敲低 TRIM52 抑制了卵巢癌细胞的侵袭、迁移和增殖，并诱导细胞凋亡。相反，在 HO8910 细胞中过表达 TRIM52 则表现出相反的结果。此外，过表达 TRIM52 增强了磷酸化 IKKβ 和 IKBα 蛋白和核蛋白 P65 的表达，这暗示了 NF-κB 信号通路的激活。敲低 TRIM52 下调了 NF-κB 信号通路下游效应物的 mRNA 和蛋白水平，包括 MMP9、Bcl2、IL8 和 TNFα，但上调了 caspase-3 的表达。这些结果表明，NF-κB 通路的激活参与了 TRIM52 在卵巢癌中的调节作用。裸鼠研究进一步证实，敲低 TRIM52 阻断了肿瘤生长，抑制了细胞增殖，并促进了细胞凋亡。我们的数据强烈表明，TRIM52 在与 NF-κB 信号通路相关的卵巢癌发展中发挥致癌作用，可能是癌症治疗的潜在靶点。
