Circ_0037078 promotes trophoblast cell proliferation, migration, invasion and angiogenesis by miR-576-5p/IL1RAP axis

Background Preeclampsia (PE) is a common hypertensive disorder of pregnancy. Recent studies have suggested that circular RNAs (circRNAs) play a pathological role in PE. Herein, this study aimed to investigate the action and mechanism of circ_0037078 in PE process. Methods The quantitative real-time PCR (qRT-PCR) and Western blot were used to determine the expression levels of RNAs and genes. Cell proliferation, migration, invasion and angiogenesis were evaluated by using cell counting kit-8 (CCK-8), colony formation, transwell, and tube formation assays, respectively. The target relation between miR-576-5p and IL1RAP (Interleukin-1 receptor accessory protein) and circ_0037078 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Results Circ_0037078 expression was higher in placental tissues of patients with PE than that of normal control. Knockdown of circ_0037078 led to an enhancement of the proliferation, migration, invasion, and angiogenesis in trophoblast cells. Mechanistically, circ_0037078 acted as a sponge for miR-576-5p, thus elevating the expression of IL1RAP, which was targeted by IL1RAP. Further rescue experiments suggested that miR-576-5p inhibition reversed the effects of circ_0037078 knockdown on above behaviors of trophoblast cells. Moreover, miR-576-5p overexpression enhanced the proliferative, migratory, invasive, angiogenic phenotypes of trophoblast cells, which were attenuated by IL1RAP up-regulation. Conclusion Circ_0037078 knockdown promotes trophoblast cell proliferation, migration, invasion, and angiogenesis in vitro by miR-576-5p/IL1RAP axis, providing a novel insight into the etiology of PE.

Automated summary

The study revealed that circ_0037078 expression level is higher in placental tissues of PE patients compared to normal controls, and knocking down circ_0037078 enhances the proliferation, migration, invasion, and angiogenesis of trophoblast cells. Mechanistically, circ_0037078 functions as a sponge for miR-576-5p, leading to increased expression of IL1RAP, which is targeted by miR-576-5p. Further experiments showed that inhibition of miR-576-5p reversed the effects of circ_0037078 knockdown on trophoblast cell behaviors.