MITA Promotes Macrophage Proinflammatory Polarization and Its circRNA-Related Regulatory Mechanism in Recurrent Miscarriage

Abstract

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.

Non-Coding RNAs: Novel Regulators of Macrophage Homeostasis in Ocular Vascular Diseases

“…Moreover, circ ITGB6 increases the stability of FGF9 mRNA by binding to IGF2BP2, which subsequently promotes M2 polarization and, consequently, induces drug resistance in ovarian cancer cells [ 58 ]. Furthermore, circ KIAA0391 has been reported to act as a miRNA sponge for the miR-512-5p/MITA axis, promoting the proinflammatory polarization and apoptosis of macrophages [ 59 ]. Due to their inherent stability, circRNAs have exhibited potential as biomarkers or therapeutic targets for immune disorders [ 60 ].…”

Identification of m6A Modification Regulated by Dysregulated circRNAs in Decidua of Recurrent Pregnancy Loss

“…Previous studies revealed that the proliferation, migration and invasion of trophoblast cells were regulated by Circ_0074371-miR-582-3p-LPR6, Circ_0011460-miR-762-HTRA1, Circ_0037078-miR-576-5p-IL1RAP and Circ_0017068-miR-330-5p-XIAP axes [11][12][13][14]. Macrophage proinflammatory polarization was regulated by the circKIAA0391-miR-512-5p-MITA axis [15]. Therefore, disturbed circRNA expression in villus and decidua may be one cause of RPL.…”