Wang Zizhao, Sun Huating, Zhu Shunpeng, Wang Fang, Li Quan, Zhou Jinhua
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Clinical Research Center of Obstetrics and Gynecology, Jiangsu Key Laboratory of Clinical Immunology of Soochow University, Suzhou, China.
Cell Death Discov. 2025 Jun 2;11(1):262. doi: 10.1038/s41420-025-02536-3.
Ovarian cancer (OC) is one of the most common and lethal solid malignancies among women, with its incidence steadily rising. Despite substantial advancements in OC research, its pathogenesis remains largely elusive. Recent studies indicate that the regulator of G protein signaling 3 (RGS3) is implicated in tumorigenesis, however, its specific role in OC development has not been extensively investigated. Herein, this research elucidated that the overexpression of RGS3 in OC correlates with adverse clinical pathological features and tumor progression. Furthermore, we demonstrated that silencing RGS3 promotes apoptosis, effectively inhibiting tumor growth and metastasis. Additionally, our findings reveal that RGS3 enhances oncogenic activity by participating in the regulation of the transforming growth factor-beta (TGF-β) pathway and corresponding epithelial-mesenchymal transition (EMT). The in-depth mechanism lies in the RGS3 facilitating the phosphorylation of SMAD2/3 by directly interacting with AT-rich interactive domain-containing protein 3B (ARID3B), which ultimately drives OC cell proliferation and metastasis. Therefore, our results position RGS3 as a significant prognostic biomarker and tumor-promoting factor in OC, underscoring the pivotal role of the RGS3/TGF-β/EMT signaling pathway in the pathogenesis of this malignancy.
卵巢癌（OC）是女性中最常见且致命的实体恶性肿瘤之一，其发病率呈稳步上升趋势。尽管卵巢癌研究取得了重大进展，但其发病机制在很大程度上仍不清楚。最近的研究表明，G蛋白信号调节因子3（RGS3）与肿瘤发生有关，然而，其在卵巢癌发展中的具体作用尚未得到广泛研究。在此，本研究阐明了RGS3在卵巢癌中的过表达与不良临床病理特征和肿瘤进展相关。此外，我们证明沉默RGS3可促进细胞凋亡，有效抑制肿瘤生长和转移。此外，我们的研究结果表明，RGS3通过参与转化生长因子-β（TGF-β）信号通路及相应的上皮-间质转化（EMT）调控来增强致癌活性。其深入机制在于RGS3通过与富含AT的相互作用结构域蛋白3B（ARID3B）直接相互作用促进SMAD2/3的磷酸化，最终驱动卵巢癌细胞增殖和转移。因此，我们的研究结果将RGS3定位为卵巢癌中一个重要的预后生物标志物和肿瘤促进因子，强调了RGS3/TGF-β/EMT信号通路在这种恶性肿瘤发病机制中的关键作用。
