Circ_0005714/miR-223-3p/ADAM9 regulatory axis affects proliferation, migration, invasion, and angiopoiesis in trophoblast cells.

Background: Circular RNAs (circRNAs) have critical roles in various types of diseases, including preeclampsia (PE). Circ_0005714 function in PE was explored in this study.

Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed for level analysis of circ_0005714, micoRNA-223-3p (miR-223-3p), and a disintegrin and metalloproteinase 9 (ADAM9). Cell Counting Kit-8 (CCK-8) and colony formation assays were used for cell viability and colony formation detection. Cell proliferation was determined by EdU assay. The determination of migration and invasion was conducted by wound healing assay and transwell assay. Tube formation assay was applied to assess angiopoiesis. Target binding analysis was performed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Western blot was used for protein examination.

Results: Circ_0005714 was highly expressed in PE placenta tissues. The expression promotion of circ_0005714 reduced proliferation, migration, invasion, and angiopoiesis in trophoblast cells. Furthermore, circ_0005714 acted as a molecular sponge for miR-223-3p and the effects of circ_0005714 on trophoblast cells were achieved by sponging miR-223-3p. Moreover, miR-223-3p could target ADAM9 and knockdown of ADAM9 reversed cell progression inhibition induced by miR-223-3p inhibitor. In addition, circ_0005714 upregulated the ADAM9 expression and inactivated the Wnt/β-catenin pathway through targeting miR-223-3p.

Conclusions: All results manifested that circ_0005714 retarded the progression of PE by mediating the miR-223-3p/ADAM9 signal network.