乳腺癌（BC）是威胁全球健康的重大问题，是女性癌症死因的主要原因。以往的证据表明，胚胎生殖细胞特异基因2（GSG2）参与了多种癌症的调控。因此，本研究调查了GSG2在BC中的临床价值、生物功能和潜在机制。通过免疫组化（IHC）、定量PCR和蛋白免疫印迹（western blotting）揭示了BC中GSG2的表达。其次，通过MTT测定法、流式细胞术、Transwell测定法和划痕愈合测定法评估了GSG2在BC中的生物功能。此外，通过共亚免疫沉淀（Co-IP）和蛋白质稳定性检测，探究GSG2调控BC进展的潜在分子机制。我们的数据显示，GSG2在BC中经常过度表达。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的沉默抑制了BC的恶性进展，表现为细胞增殖减少、凋亡增强和肿瘤生长减缓。GSG2沉默减少了BC细胞的迁移活力，通过上皮-间质转化（EMT）实现，如Vimentin和Snail的下调。此外，E2F转录因子1（E2F1）被视为GSG2的靶蛋白，降低E2F1减弱了GSG2对BC细胞的促进作用。机制上，GSG2的沉默加速了E2F1蛋白的泛素化，而泛素化是由E3泛素连接酶MDM2介导的。通过MDM2介导的E2F1泛素化，GSG2促进了BC的发展和进展，可能成为一个具有潜在治疗价值的有前景的靶点。© 2023年。BioMed Central Ltd.成为Springer Nature一部分。

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.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.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.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.© 2023. BioMed Central Ltd., part of Springer Nature.