Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China.
Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Zhejiang Province Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Int J Biol Macromol. 2024 Nov;281(Pt 2):136318. doi: 10.1016/j.ijbiomac.2024.136318. Epub 2024 Oct 5.
Aberrantly expressed circRNAs affects various anti-tumour immune responses and immune cell regulation. However, the exact function of circGLIS2 on the pathogenesis of EMs remains unclear. In this study, we found that circGLIS2 was upregulated in EMs tissues and intimately related to clinicopathologic characteristics of EMs patients. Functionally, IHC and mouse model of EMs proved that circGLIS2 recruited immune cells infiltrated into ectopic endometrial microenvironment. RNA-seq, ELISA, RT-qPCR, and western blot results indicated that circGLIS2 influenced immune infiltration by regulating IL-1β. Besides, expression of circGLIS2 and IL-1β was also closely correlated in 284 human endometrium tissues. Mechanistically, RNA sequencing and intermolecular interaction prediction established "circGLIS2-miR-4731-5p-IL-1β" network. RNA pull down, RIP, dual luciferase reporter assay and expression regulation analysis confirmed the interaction among "circGLIS2-miR-4731-5p-IL-1β" axis. In summary, our findings demonstrated that circGLIS2 facilitated EMs progression by increasing immune cell infiltration via miR-4731-5p/IL-1β axis.
异常表达的 circRNAs 影响各种抗肿瘤免疫反应和免疫细胞调节。然而,circGLIS2 对 EMs 发病机制的确切功能仍不清楚。在本研究中,我们发现 circGLIS2 在 EMs 组织中上调,并与 EMs 患者的临床病理特征密切相关。免疫组化和 EMs 小鼠模型证明,circGLIS2 募集免疫细胞浸润到异位子宫内膜微环境中。RNA-seq、ELISA、RT-qPCR 和 Western blot 结果表明,circGLIS2 通过调节 IL-1β 影响免疫浸润。此外,在 284 个人类子宫内膜组织中,circGLIS2 和 IL-1β 的表达也密切相关。在机制上,RNA 测序和分子间相互作用预测建立了“circGLIS2-miR-4731-5p-IL-1β”网络。RNA 下拉、RIP、双荧光素酶报告基因测定和表达调控分析证实了“circGLIS2-miR-4731-5p-IL-1β”轴之间的相互作用。总之,我们的研究结果表明,circGLIS2 通过 miR-4731-5p/IL-1β 轴增加免疫细胞浸润促进 EMs 的进展。