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  • Title: MiR-221-3p is down-regulated in preeclampsia and affects trophoblast growth, invasion and migration partly via targeting thrombospondin 2.
    Author: Yang Y, Li H, Ma Y, Zhu X, Zhang S, Li J.
    Journal: Biomed Pharmacother; 2019 Jan; 109():127-134. PubMed ID: 30396069.
    Abstract:
    Preeclampsia (PE) is a common obstetrical disorder characterized by hypertension and proteinuria. The aberrant expression of miR-221-3p in placental tissues has been implicated in the pathogenesis of PE. This study examined the role of miR-221-3p in trophoblast growth, invasion and migration, and explored the underlying mechanisms. Our results showed that miR-221-3p was down-regulated in placental tissues from PE patients compared to heathy controls as measured by quantitative real-time PCR assay. CCK-8 assay, Transwell invasion assay and wound healing assay showed that miR-221-3p overexpression promoted trophoblast (HTR-8/SVneo cells) growth, invasion and migration, and knockdown of miR-221-3p exerted the opposite effects. Flow cytometry experiments further demonstrated that miR-221-3p overexpression inhibited apoptosis, increased cell population at S phase, and decreased cell population at G0/G1 phase of HTR-8/SVneo cells; while miR-221-3p knockdown exerted the opposite effects. Bioinformatics prediction and luciferase reporter assay showed that miR-221-3p targeted the 3' untranslated region of thrombospondin 2 (THBS2), and qRT-PCR and western blot assays revealed that miR-221-3p negatively regulated the expression of THBS2 in HTR-8/SVneo cells. Furthermore, overexpression of THBS2 attenuated the in vitro effects of miR-221-3p overexpression on cell growth, invasion and migration of HTR-8/SVneo cells. The clinical sample analysis showed that the mRNA expression levels of THBS2 was significantly increased in placental tissues from PE patients and was negatively correlated with expression levels of miR-221-3p. In summary, our results demonstrated that miR-221-3p was down-regulated in PE, and the in vitro functional assays revealed that miR-221-3p promoted trophoblast growth, invasion and migration partly via targeting THBS2.
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