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WNT6 通过上调/激活典型的 Wnt 通路和 Notch1 信号通路参与卵巢癌的发生和发展。

WNT6 participates in the occurrence and development of ovarian cancer by upregulating/activating the typical Wnt pathway and Notch1 signaling pathway.

机构信息

Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.

Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; China Medical University, Shenyang 110001, China.

出版信息

Gene. 2022 Dec 20;846:146871. doi: 10.1016/j.gene.2022.146871. Epub 2022 Sep 6.

DOI:10.1016/j.gene.2022.146871
PMID:36075327
Abstract

Wnt/β-catenin pathway is associated with the progression of various cancers such as gastric cancer, colorectal cancer, and endometrial cancer. Using the Kaplan-Meier Plotter database, we found that WNT6 was associated with progression-free survival (PFS) outcomes. Immunohistochemical analysis of ovarian cancer samples and normal ovaries showed that the expression of WNT6 protein was significantly increased in ovarian cancer samples. Further, we explored the possible role of WNT6 in the occurrence and development of ovarian cancer. Our results showed that the mRNA and protein expression of WNT6 were significantly higher in CAOV3 and OVCAR3 cells compared with other ovarian cancer cell lines and normal ovarian cell line IOSE-80 as well. The transformation of CAOV3 and OVCAR3 cells with short interfering WNT6 (siWNT6) significantly inhibited their proliferation and lamellipodia formation, causing cell cycle arrest and promoting cell apoptosis. Western blot experiments confirmed that the down-regulation of WNT6 inhibited the expression of β-catenin and Notch1. These results suggest that WNT6 plays an important role in the occurrence and development of ovarian cancer.

摘要

Wnt/β-catenin 通路与多种癌症的进展有关,如胃癌、结直肠癌和子宫内膜癌。我们使用 Kaplan-Meier Plotter 数据库发现 WNT6 与无进展生存期(PFS)结果相关。对卵巢癌样本和正常卵巢的免疫组织化学分析表明,WNT6 蛋白的表达在卵巢癌样本中显著增加。此外,我们探讨了 WNT6 在卵巢癌发生和发展中的可能作用。我们的结果表明,WNT6 的 mRNA 和蛋白表达在 CAOV3 和 OVCAR3 细胞中明显高于其他卵巢癌细胞系和正常卵巢细胞系 IOSE-80。用短发夹 RNA(siWNT6)转染 CAOV3 和 OVCAR3 细胞可显著抑制其增殖和片状伪足形成,导致细胞周期停滞并促进细胞凋亡。Western blot 实验证实,下调 WNT6 抑制了β-catenin 和 Notch1 的表达。这些结果表明,WNT6 在卵巢癌的发生和发展中起着重要作用。

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