The Role of STAT-3 and IL-26 Signaling Pathways in Leiomyoma Pathophysiology

Şenol Şentürk, Mehmet Kağıtçı, Tolga Mercantepe, Recep Bedir, Nalan Kuruca
In: Journal of Clinical Medicine · 2025 · vol. 14(17) , pp. 6021 · doi:10.3390/jcm14176021 · PMID:40943781 · PMC12429334 · W4413627758
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STAT-3 and IL-26 are significantly upregulated in uterine leiomyomas compared to normal myometrium, suggesting their involvement in tumor growth and progression.

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Abstract

Background: Uterine leiomyomas are the most common pelvic tumors in women of reproductive age. There is no clear conclusion in the literature regarding the pathophysiology of these conditions. STAT proteins stimulate the transcription of target genes. STAT-3 leads to an increase in VEGF levels and plays a role in tumorigenesis. IL-26 and other cytokines are vital immune response mediators. Cytokine dysregulation affects the immune response of various organs and tissues, making them prone to various diseases, such as inflammation, infection, and tumors. Methods: In the present study, we aimed to determine whether STAT-3 and IL-26 play a role in the development of uterine leiomyoma. This case–control study included 38 patients who underwent hysterectomy due to uterine leiomyoma and 30 patients who underwent hysterectomy due to non-organic benign gynecological causes other than myoma. Sections from the myometrium of the control group and the leiomyoma tissue of the case group were subjected to immunohistochemical staining for STAT-3 and IL-26. Results: When the uterine tissue sections of the control group incubated with STAT-3 were examined under a light microscope, the smooth muscle and fibroblast cells in the myometrium were STAT-3-negative, while the number of smooth muscle and fibroblast cells showing strong STAT-3-staining in the leiomyoma sections was high. When the uterine tissue sections incubated with IL-26 were examined under a light microscope, the normal smooth muscle and fibroblast cells in the control group were IL-26-negative, while there was an increase in the number of cells showing strong IL-26-staining in the leiomyoma smooth muscle and fibroblast cells. Conclusions: Our findings show that STAT-3 and IL-26 levels are significantly increased in uterine leiomyomas, and this increase may play a role in the growth and progression of uterine fibroids. The current results may enable the development of innovative treatment options, as they demonstrate the role of novel pathways in the formation of uterine fibroids.

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