Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, China.
Int J Mol Sci. 2023 May 31;24(11):9545. doi: 10.3390/ijms24119545.
MITA (also called STING), a master regulator of DNA-mediated innate immune activation, is a potential therapeutic target for viral infection and virus-related diseases. The circRNA-mediated ceRNA network plays important roles in gene regulation and may contribute to many human diseases. However, the relationship between MITA and recurrent miscarriage (RM) and its circRNA-related regulatory mechanisms remain unclear. In this study, we validated that the decidual M1/M2 ratio was upregulated in RM patients, suggesting the vital roles of decidual macrophages in the pathogenesis of RM. We found that MITA was highly expressed in decidual macrophages of RM patients and validated that MITA could promote apoptosis and macrophage proinflammatory polarization in THP-1-derived macrophage (TDM) cells. Using circRNA sequencing and bioinformatic analysis, we screened out a novel circRNA (circKIAA0391) that is overexpressed in decidual macrophages of RM patients. Mechanistically, we found that circKIAA0391 could promote the apoptosis and proinflammatory polarization of TDM cells by sponging the miR-512-5p/MITA axis. This study provides a theoretical basis for further understanding the impact of MITA on macrophages and its circRNA-related regulatory mechanisms, which may have a crucial immunomodulatory function in the pathophysiology of RM.
MITA（也称为 STING）是 DNA 介导的固有免疫激活的主要调节剂，是病毒感染和病毒相关疾病的潜在治疗靶标。circRNA 介导的 ceRNA 网络在基因调控中发挥重要作用，可能与许多人类疾病有关。然而，MITA 与复发性流产（RM）及其 circRNA 相关的调节机制之间的关系尚不清楚。在这项研究中，我们验证了 RM 患者的蜕膜 M1/M2 比值上调，表明蜕膜巨噬细胞在 RM 发病机制中的重要作用。我们发现 MITA 在 RM 患者的蜕膜巨噬细胞中高表达，并验证了 MITA 可以促进 THP-1 衍生的巨噬细胞（TDM）细胞中的凋亡和巨噬细胞促炎极化。通过 circRNA 测序和生物信息学分析，我们筛选出一种在 RM 患者的蜕膜巨噬细胞中过度表达的新型 circRNA（circKIAA0391）。从机制上讲，我们发现 circKIAA0391 通过海绵吸附 miR-512-5p/MITA 轴来促进 TDM 细胞的凋亡和促炎极化。这项研究为进一步了解 MITA 对巨噬细胞及其 circRNA 相关调节机制的影响提供了理论基础，这可能在 RM 的病理生理学中具有关键的免疫调节功能。
