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 weredetected 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.