CircCRIM1 mediates proliferation, migration, and invasion of trophoblast cell through regulating miR-942-5p/IL1RAP axis

Abstract

Background: Preeclampsia (PE) is a severe complication that occurs during pregnancy and a main cause of perinatal mortality of mothers as well as infants, which is characterized by abnormal placental trophoblast. Previous study reported that aberrant circular RNA (circRNA) was involved in the pathogenesis and progression of PE. Herein, we aimed to investigate the role of circCRIM1 and explore the mechanism of circCRIM1 in PE.

Methods: The quantitative real-time PCR (qRT-PCR) was conducted to determine the relative expression of circCRIM1, miR-942-5p, and IL1RAP in tissues and cells. Cell proliferation viability was assessed by both MTT and EdU assays. Cell cycle distribution was analyzed using flow cytometry. Transwell assay was performed to test the cell migration and invasion. The protein levels of CyclinD1, MMP9, MMP2, and IL1RAP were measured by western blot. The putative binding sites between miR-942-5p and circCRIM1 or IL1RAP 3'UTR were verified by dual-luciferase reporter gene assay. Rescue experiment was performed to confirm that miR-942-5p/IL1RAP axis was functional target of circCRIM1 in trophoblast cells.

Results: CircCRIM1 was upregulated in placenta tissues of PE and its expression was inversely related to infant weight. Overexpression of circCRIM1 suppressed proliferation, migration, and invasion and reduced the protein levels of CyclinD1, MMP9, MMP2 of trophoblast cells, whereas its knockdown exerted the opposite effect. CircCRIM1 could interact with miR-942-5p, and introduction of miR-942-5p partially abated the inhibitory effect of circCRIM1 on trophoblast cell behaviors. IL1RAP was directly targeted and negatively regulated by miR-942-5p. miR-942-5p played its regulatory role on cell proliferation, migration, and invasion of trophoblast by IL1RAP. Further analysis showed that circCRIM1 modulated IL1RAP expression via sponging miR-942-5p.

Conclusion: The results of the present study demonstrated that circCRIM1 inhibited the proliferation, migration, and invasion of trophoblast cells through sponging miR-942-5p and up-regulating IL1RAP, providing a possible new mechanism of PE.

Keywords: IL1RAP; circCRIM1; miR-942-5p; preeclampsia; trophoblast cell.