GSG2 通过 MDM2 介导的 E2F1 泛素化促进人类乳腺癌的进展。
GSG2 facilitates the progression of human breast cancer through MDM2-mediated ubiquitination of E2F1.
机构信息
Day Ward, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No. 44 Xianheyan Road, Shenyang, 110042, China.
Department of Breast Surgery, Qilu Hospital of Shandong University, No. 107 Wenhuaxi Road, Jinan, 250012, Shandong, China.
出版信息
J Transl Med. 2023 Aug 3;21(1):523. doi: 10.1186/s12967-023-04358-2.
BACKGROUND
Breast cancer (BC) has posed a great threat to world health as the leading cause of cancer death among women. Previous evidence demonstrated that germ cell-specific gene 2 (GSG2) was involved in the regulation of multiple cancers. Thus, the clinical value, biological function and underlying mechanism of GSG2 in BC were investigated in this study.
METHODS
The expression of GSG2 in BC was revealed by immunohistochemistry (IHC), qPCR and western blotting. Secondly, the biological function of GSG2 in BC was evaluated by MTT assay, flow cytometry, Transwell assay and wound healing assay. Furthermore, the potential molecular mechanism of GSG2 regulating the progression of BC by co-immunoprecipitation (Co-IP) and protein stability detection.
RESULTS
Our data indicated that GSG2 was frequently overexpressed in BC. Moreover, there was a significant correlation between the GSG2 expression and the poor prognosis of BC patients. Functionally, GSG2 knockdown inhibited the malignant progression of BC characterized by reduced proliferation, enhanced apoptosis and attenuated tumor growth. Migration inhibition of GSG2 knockdown BC cells via epithelial-mesenchymal transition (EMT), such as downregulation of Vimentin and Snail. In addition, E2F transcription factor 1 (E2F1) was regarded as a target protein of GSG2. Downregulation of E2F1 attenuated the promoting role of GSG2 on BC cells. Mechanistically, knockdown of GSG2 accelerated the ubiquitination of E2F1 protein, which was mediated by E3 ubiquitin ligase MDM2.
CONCLUSIONS
GSG2 facilitated the development and progression of BC through MDM2-mediated ubiquitination of E2F1, which may be a promising candidate target with potential therapeutic value.
背景
乳腺癌（BC）作为女性癌症死亡的主要原因，对世界健康构成了巨大威胁。先前的证据表明，生殖细胞特异性基因 2（GSG2）参与了多种癌症的调控。因此，本研究探讨了 GSG2 在 BC 中的临床价值、生物学功能和潜在机制。
方法
通过免疫组织化学（IHC）、qPCR 和 Western blot 揭示 GSG2 在 BC 中的表达。其次，通过 MTT 测定、流式细胞术、Transwell 测定和划痕愈合测定评估 GSG2 在 BC 中的生物学功能。此外，通过免疫共沉淀（Co-IP）和蛋白质稳定性检测来研究 GSG2 调节 BC 进展的潜在分子机制。
结果
我们的数据表明，GSG2 在 BC 中频繁过表达。此外，GSG2 表达与 BC 患者的不良预后之间存在显著相关性。功能上，GSG2 敲低抑制了 BC 的恶性进展，特征为增殖减少、凋亡增强和肿瘤生长减弱。GSG2 敲低的 BC 细胞通过上皮-间充质转化（EMT）抑制迁移，如波形蛋白和 Snail 的下调。此外，E2F 转录因子 1（E2F1）被认为是 GSG2 的靶蛋白。E2F1 的下调减弱了 GSG2 对 BC 细胞的促进作用。机制上，GSG2 的敲低加速了 E3 泛素连接酶 MDM2 介导的 E2F1 蛋白泛素化。
结论
GSG2 通过 MDM2 介导的 E2F1 泛素化促进了 BC 的发展和进展，这可能是一种有前途的候选治疗靶点，具有潜在的治疗价值。
Zotero 插件