Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China.
Hum Cell. 2022 Nov;35(6):1824-1837. doi: 10.1007/s13577-022-00767-5. Epub 2022 Aug 14.
Zinc-finger transcription factor odd-skipped related 1 (OSR1) is involved in the progression of certain types of cancers, via regulating the transcription of downstream genes. However, the function of OSR1 in ovarian cancer (OC) progression remains unclear. The present study aimed to explore the OSR1 expression pattern in OC tissues and cell lines. Functional assays were performed to explore the regulatory effects of OSR1 on OC cell growth, migration and invasion in vitro and in vivo. Results of the present study demonstrated that OSR1 was significantly downregulated in OC tissues compared with healthy ovarian tissues (P < 0.01). Moreover, SKOV-3 and OVCAR-3 cells with low OSR1 expression were used for functional studies, and results demonstrated that OSR1 overexpression suppressed cell growth by inhibiting cell cycle progression and inducing cell apoptosis in vitro. OC cells with higher OSR1 expression levels exhibited reduced levels of migration and invasion, when compared with the corresponding control. In addition, OSR1 expression in xenografts models resulted in diminished tumor volume and suppressed tumorigenesis. OSR1 enhanced follistatin-like protein 1 (FSTL1) expression at the transcriptional level through directly binding to the promoter of FSTL1, which was commonly reported to exert a tumor suppressor role in OC progression. Moreover, FSTL1 knockdown reversed the action of OSR1 overexpression in OC progression, including cell viability, migration, invasion, and apoptosis. In conclusion, these results indicated that OSR1 may function as a tumor suppressor through augmenting FSTL1 transcription in OC progression, suggesting that the OSR1/ FSTL1 axis may exhibit potential as a therapeutic target for OC therapy.
锌指转录因子 odd-skipped 相关 1（OSR1）通过调节下游基因的转录参与某些类型癌症的进展。然而，OSR1 在卵巢癌（OC）进展中的作用尚不清楚。本研究旨在探讨 OSR1 在 OC 组织和细胞系中的表达模式。进行功能测定以探讨 OSR1 对 OC 细胞体外和体内生长、迁移和侵袭的调节作用。本研究结果表明，OSR1 在 OC 组织中的表达明显低于健康卵巢组织（P<0.01）。此外，使用低 OSR1 表达的 SKOV-3 和 OVCAR-3 细胞进行功能研究，结果表明 OSR1 过表达通过抑制细胞周期进程和诱导细胞凋亡来抑制体外细胞生长。与相应对照相比，OSR1 表达水平较高的 OC 细胞的迁移和侵袭水平降低。此外，异种移植模型中的 OSR1 表达导致肿瘤体积减小并抑制肿瘤发生。OSR1 通过直接结合 FSTL1 启动子在转录水平上增强卵泡抑素样蛋白 1（FSTL1）的表达，FSTL1 通常被报道在 OC 进展中发挥肿瘤抑制作用。此外，FSTL1 敲低逆转了 OSR1 过表达在 OC 进展中的作用，包括细胞活力、迁移、侵袭和凋亡。总之，这些结果表明，OSR1 可能通过增强 OC 进展中的 FSTL1 转录来发挥肿瘤抑制作用，这表明 OSR1/FSTL1 轴可能作为 OC 治疗的潜在治疗靶点。
