Yu Yakun, Yao Yilin, Liu Yan, Sun Ying, Feng Haoyuan, Kong Nana, Chen Rui, Wu Mingqi, Guo Shuaitian, Tian Shen, Zhang Cheng
College of Life Science, Capital Normal University, Beijing, 100048, People's Republic of China.
Center for Assisted Reproductive Medicine, Department of Obstetrics and Gynecology, the Sixth Medical Center of Chinese PLA General Hospital, Beijing, 100048, People's Republic of China.
Reprod Sci. 2025 May;32(5):1545-1556. doi: 10.1007/s43032-024-01721-6. Epub 2024 Oct 15.
Ovarian cancer is a common malignant tumor in the female reproductive system, and Granulosa cell tumor (GCT) of the ovary is a rare type of ovarian cancer, which significantly threatens women's reproductive health. It has been reported that dysregulation of thyroid hormones (THs) may be closely related to the progression and prognosis of ovarian cancer. Moreover, THs regulate phosphorylation of signal transducer and activator of transcription (STAT3) and Octamer-binding transcription factor 4 (OCT4) expression. It has been reported that STAT3 and OCT4 play important roles in cellular development and tumorigenesis. However, the mechanisms by which THs affect the development of GCT are still remained unclear. To evaluate the effect of THs on human ovarian granulosa tumor cells (KGN), cells were treated with 3,5,3' -triiodothyronine (T). Oct4 small interfering (Oct4 siRNA) or STAT3 inhibitor C188-9 was also co-cultured with cells in some experiments, respectively. The cell viability, proliferation, and proteins content were detected by CCK-8, EdU, and Western Blotting, respectively. The results showed that T enhanced cell viability and proliferation. Moreover, T also increased the expression of thyroid hormone receptor (TR), p-STAT3, and OCT4 proteins. The effects of T on both p-STAT3 and OCT4 expression were blocked by TR antagonist 1-850. Meanwhile, C188-9, an inhibitor of STAT3, decreased T-induced cellular viability, proliferation, and OCT4 expression, highlighting that p-STAT3 can regulate the expression of OCT4 and affect cellular viability, and proliferation. Furthermore, T-induced cellular growth was reduced by Oct4 siRNA, which indicates that T regulates cellular development through OCT4. These findings suggest that T increases cellular development via OCT4, which is mediated by phosphorylation of STAT3, and TR is also involved in these processes.
卵巢癌是女性生殖系统中常见的恶性肿瘤，而卵巢颗粒细胞瘤（GCT）是一种罕见的卵巢癌类型，严重威胁女性生殖健康。据报道，甲状腺激素（THs）失调可能与卵巢癌的进展和预后密切相关。此外，THs调节信号转导和转录激活因子（STAT3）的磷酸化以及八聚体结合转录因子4（OCT4）的表达。据报道，STAT3和OCT4在细胞发育和肿瘤发生中起重要作用。然而，THs影响GCT发展的机制仍不清楚。为了评估THs对人卵巢颗粒细胞瘤细胞（KGN）的影响，用3,5,3'-三碘甲状腺原氨酸（T）处理细胞。在一些实验中，Oct4小干扰RNA（Oct4 siRNA）或STAT3抑制剂C188-9也分别与细胞共培养。分别通过CCK-8、EdU和蛋白质免疫印迹法检测细胞活力、增殖和蛋白质含量。结果表明，T增强了细胞活力和增殖。此外，T还增加了甲状腺激素受体（TR）、磷酸化STAT3和OCT4蛋白的表达。TR拮抗剂1-850阻断了T对磷酸化STAT3和OCT4表达的影响。同时，STAT3抑制剂C188-9降低了T诱导的细胞活力、增殖和OCT4表达，突出表明磷酸化STAT3可调节OCT4的表达并影响细胞活力和增殖。此外，Oct4 siRNA降低了T诱导的细胞生长，这表明T通过OCT4调节细胞发育。这些发现表明，T通过OCT4增加细胞发育，这是由STAT3的磷酸化介导的，TR也参与了这些过程。
