Researcher / - Seoul National University College of Medicine, Republic of Korea
Introduction/Rationale: This study explores the potential of Interleukin-22 receptor alpha (IL-22Rα) as a therapeutic target for gynecologic cancer. Gynecologic cancers, including cervical cancer and ovarian cancer, are closely associated with chronic inflammation. Interleukin (IL)-22, a pro-inflammatory cytokine involved in epithelial regeneration, has emerged as a critical mediator linking inflammatory signaling to oncogenic processes.
Methods: We investigated the functional role of IL-22/IL-22Rα signaling in cervical and ovarian cancer models by CCK-8 assay, cell cycle analysis, and Western blotting. Furthermore, IL-22Rα‒knockdown cell lines were established to determine whether the proliferative effects were specifically mediated through IL-22/IL-22Rα signaling.
Results: IL-22 stimulation enhanced proliferation of cervical cancer cell lines (CaSki and HeLa) and ovarian cancer cell lines (SK-OV-3 and NIH:OVCAR-3) by promoting S and G2/M phase progression. This effect was accompanied by upregulation of cell cycle‒associated cyclins, including A, B1, D1, and E1, without distinct changes in cyclin‒dependent kinase expressions. Genetic suppression of IL-22Rα abrogated IL-22‒induced signaling activation, cell cycle progression, and proliferation in vitro. Consistently, IL-22Rα suppression markedly inhibited IL-22‒driven tumor growth in cervical cancer and ovarian cancer xenograft models.
Conclusion: Our findings identify the IL-22/IL-22Rα axis as a key inflammation‒driven regulator of tumor proliferation in gynecologic cancers and reveal the potential therapeutic target of IL-22Rα.
