Hsa_circ_0088196 suppresses trophoblast migration and invasion by the miR‐525‐5p/ABL1 axis and the PI3K/AKT signaling pathway

Abstract Our study aimed to explore the role of circ_0088196 (circular TNC [circTNC]) in trophoblast invasion and migration in preeclampsia (PE) both in vitro and in vivo. CircTNC, miR‐525‐5p, and ABL1 expression in trophoblast HTR8/SVneo cells were evaluated by quantitative real‐time polymerase chain reaction (qRT‐PCR). Cell viability, migration, and invasion were detected by Cell Counting Kit‐8 (CCK‐8), wound healing, and Transwell assays. The binding between circTNC (or ABL1) and miR‐525‐5p was validated by RNA pulldown and luciferase reporter assays. The mouse model of PE was injected with sh‐circTNC and the effects of circTNC knockdown on the mean artery pressure, urine protein concentration, and fetal survival number of pregnant mice were examined. The expression of MMP‐2, MMP‐9, and PI3K/AKT pathway molecules in placental tissues was assessed by immunohistochemistry, qRT‐PCR, and western blot analysis. CircTNC overexpression inhibited cell invasion and migration, but did not influence cell proliferation. CircTNC bound with miR‐525‐5p, whose knockdown repressed cell invasion and migration, while it exerted no effect on cell proliferation. ABL1, a target of miR‐525‐5p, attenuated cell migration and invasion, without influence on cell viability. Importantly, either miR‐525‐5p overexpression or ABL1 depletion antagonized the repression of upregulated circTNC on trophoblast cell migration and invasion, MMP‐2 and MMP‐9 expression, and the PI3K/AKT pathway. CircTNC knockdown alleviated PE symptoms in pregnant mice. CircTNC knockdown promoted the trophoblast invasiveness in mice placenta by upregulating MMP‐2/9 expression and suppressing the PI3K/AKT pathway. Circ_0088196 represses trophoblast invasion and migration both in vitro and in vivo via regulating the miR‐525‐5p/ABL1 axis and activating the PI3K/AKT pathway.