Circ_0111277 suppresses trophoblast cell proliferation, angiogenesis, migration, invasion and EMT via regulating miR-188-3p/GRHL2 axis

Problem: Preeclampsia (PE) is the main factor threatening the life of primipara. Defective migration and invasion of trophoblast cells was one of the causes of PE. Circ_0111277 had been reported to be related to the development of PE, but the mechanism of its effect on trophoblast cells needed further study.

Method of study: The expression of circ_0111277, microRNA-188-3p (miR-188-3p) and grainyhead-like 2 (GRHL2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-20-deoxyuridine (EdU) and colony formation assay were used to examine cell proliferation ability. Tube formation and transwell assay were performed to assess the angiogenesis and metastasis ability of cells. Western blot was applied to measure the levels of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and Vimentin) and GRHL2 protein. The relationship between miR-188-3p and circ_0111277 or GRHL2 was verified by the dual luciferase reporter experiment.

Results: Circ_0111277 and GRHL2 were elevated, and miR-188-3p was declined in PE patients. Overexpression of circ_0111277 could inhibit the proliferation, angiogenesis, migration, invasion and EMT of trophoblast cells (HTR-8/Svneo). Circ_0111277 was the molecular sponge of miR-188-3p. MiR-188-3p up-regulation could reduce the inhibition of HTR-8/Svneo cell growth caused by overexpression of circ_0111277. GRHL2 was a target gene of miR-188-3p, and GRHL2 silencing relieved the adverse effects of miR-188-3p inhibitors on HTR-8/Svneo. In general, circ_0111277 up-regulated GRHL2 expression through sponge miR-188-3p.

Conclusion: Highly expressed circ_0111277 up-regulated the expression of GRHL2 through sponge miR-188-3p, thereby inhibiting trophoblast cells function, which suggested a new molecular mechanism for the pathogenesis of PE.