Effects of Thyroid Hormones on Cellular Development in Human Ovarian Granulosa Tumor Cells (KGN).

Abstract

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 (T₃). 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 T₃ enhanced cell viability and proliferation. Moreover, T₃ also increased the expression of thyroid hormone receptor (TR), p-STAT3, and OCT4 proteins. The effects of T₃ on both p-STAT3 and OCT4 expression were blocked by TR antagonist 1-850. Meanwhile, C188-9, an inhibitor of STAT3, decreased T₃-induced cellular viability, proliferation, and OCT4 expression, highlighting that p-STAT3 can regulate the expression of OCT4 and affect cellular viability, and proliferation. Furthermore, T₃-induced cellular growth was reduced by Oct4 siRNA, which indicates that T₃ regulates cellular development through OCT4. These findings suggest that T₃ increases cellular development via OCT4, which is mediated by phosphorylation of STAT3, and TR is also involved in these processes.