Interleukin-22 promotes endometrial carcinoma cell proliferation and cycle progression via ERK1/2 and p38 activation

作者：Shiqi Liu, Ruqian Zhao, Yuqin Zang, Pengzhu Huang, Qiaoling Zhang, Xiangqin Fan, Junyi Bai, Xingyu Zheng, Shuangshuang Zhao, Dan Kuai, Chao Gao, Yingmei Wang, Fengxia Xue · 发表于：Molecular and Cellular Biochemistry · 年份：2024 · DOI：10.1007/s11010-024-05179-7 · 被引用次数：7 · 研究领域：Cytokine Signaling Pathways and Interactions、Immune Cell Function and Interaction、Psoriasis: Treatment and Pathogenesis

Endometrial carcinoma (EC) is one of the most common gynecological malignant tumors, but its underlying pathogenic mechanisms are largely obscure. Interleukin-22 (IL-22), one cytokine in the tumor immune microenvironment, was reported to be associated with carcinoma progression. Here, we aimed to investigate the regulation of IL-22 in endometrial carcinoma. Enzyme-linked immunosorbent assay (ELISA) analysis of IL-22 was done in 27 controls and 51 patients with EC. We examined the proliferative potential, cycle progression, and signaling pathways modulated by IL-22 in EC cells. Western blot analysis was performed to investigate the expression of proliferative and cycle-related proteins in EC cells. The effect of IL-22 mediated by interleukin-22 receptor alpha 1 (IL-22RA1) was examined using cell transfection with small interfering RNA (siRNA). In addition, a xenograft tumor model was performed to assess the effect of IL-22 in vivo. We demonstrated significant up-regulation of serum IL-22 concentrations in EC patients (42.59 ± 23.72 pg/mL) compared to the control group (27.47 ± 8.29 pg/mL). High levels of IL-22 concentrations appear to correlate with malignant clinicopathological features of EC. Treatment with IL-22 promoted cell proliferation and G1/S phase progression in Ishikawa and HEC-1B cells. Western blot analysis revealed that c-Myc, cyclin E1, cyclin-dependent kinase (CDK)2, cyclin D1, CDK4, CDK6, p-extracellular signal-regulated kinase1/2 (p-ERK1/2), and p-p38 were hi...