Circular RNA hsa_circ_0026552 inhibits the proliferation, migration and invasion of trophoblast cells via the miR-331-3p/TGF-βR1 axis in pre-eclampsia

Globally, pre-eclampsia (PE) is a gestational disorder that causes increased morbidity of the fetus and mortality induced by pregnancy. Despite various studies, the understanding of the causes or mechanism of the development of PE remains elusive. Thus, the present study aimed to investigate the role of circular (circ)RNA hsa_circ_0026552 (hsa_circ_0026552) in the development of PE and its mechanism of regulation. hsa_circ_0026552 differential expression in PE tissue data and clinical samples were analyzed and it was observed that hsa_circ_0026552 is highly upregulated in PE samples. Furthermore, miR-331-3p was detected as an hsa_circ_0026552 target miRNA and TGF-βR1 gene as a target of miR-331-3p. These results were confirmed using various assays, including dual-luciferase reporter, reverse transcription-quantitative PCR and RNA pull-down assay. It was observed that miR-331-3p expression was negatively correlated to hsa_circ_0026552 relative expression, while TGF-βR1 expression was positively correlated to hsa_circ_0026552 expression evaluated by Pearson's correlation test. The functional experiments, including Cell Counting Kit-8, colony formation and Transwell assay, showed that silencing hsa_circ_0026552 could significantly strengthen the proliferation, migration and invasion of the trophoblastic HTR-8/SVneo cells, but the subsequent overexpression of hsa_circ_0026552 reversed this. Mechanistically, it was concluded that hsa_circ_0026552 acts as a miR-331-3p sponge to upregulate TGF-βR1 expression in trophoblasts and is involved significantly in PE development and progression in pregnant women. The circRNA hsa_circ_0026552 could be a novel therapeutic target and prognostic biomarker for PE.