Abstract
This research evaluated the effects of miR-218-5p on trophoblast infiltration and endoplasmic reticulum/oxidative stress during preeclampsia (PE). The expression of miR-218-5p and special AT-rich sequence binding protein 1 (SATB1) in placental tissues from 25 patients with PE and 25 normal pregnant subjects was determined using qRT-PCR and western blotting. Cell invasion and cell migration were detected by performing Transwell assays and scratch assays, respectively. MMP-2/9, TIMP1/2, HIF-1α, p-eIF2α, and ATF4 expression in cells was assessed through western blotting. Intracellular reactive oxygen species were detected using 2,7-dichlorodihydrofluorescein diacetate, and intracellular malondialdehyde and superoxide dismutase activities were determined with kits. Dual-luciferase and RNA pull-down assays were performed to verify the interaction between miR-218-5p and UBE3A. Co-immunoprecipitation and western blotting were used to detect the ubiquitination levels of SATB1. A rat model of PE was established, and an miR-218-5p agomir was injected into rat placental tissues. The pathological characteristics of placental tissues were detected via HE staining, and MMP-2/9, TIMP1/2, p-eIF2α, and ATF4 expression in rat placental tissues was determined through western blotting. MiR-218-5p and SATB1 were expressed at low levels, while UBE3A was highly expressed in the placental tissues of patients with PE. The transfection of an miR-218-5p mimic, UBE3A shRNA, or an SATB1 overexpression vector into HTR-8/SVneo cells promoted trophoblast infiltration and inhibited endoplasmic reticulum/oxidative stress. It was determined that UBE3A is a target of miR-218-5p; UBE3A induces ubiquitin-mediated degradation of SATB1. In PE model rats, miR-218-5p alleviated pathological features, promoted trophoblast infiltration, and inhibited endoplasmic reticulum/oxidative stress. MiR-218-5p targeted and negatively regulated UBE3A expression to inhibit ubiquitin-mediated SATB1 degradation, promote trophoblast infiltration, and inhibit endoplasmic reticulum/oxidative stress.
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We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.
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This work was supported by the Taishan Scholar Foundation of Shandong Province (Grant No. tsqn202103181), National Natural Science Foundation of China (Grant No. 81801473; 81971409; 81741037), and Jinan Science and Technology Bureau (Grant No. 201907011).
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LL conceived the ideas; designed the experiments. GX and SXM performed the experiments. GX; SXM and YYL analyzed the data. GX and SXM provided critical materials. GX; SXM and YYL wrote the manuscript. LL supervised the study. All the authors have read and approved the final version for publication.
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Written informed consent was acquired from the subjects or their families for the acquisition and use of all study samples. All study protocols were approved by the Ethics Committee of the Shandong Provincial Hospital Affiliated to Shandong First Medical University (Approval Number: 2019–238) and in accordance with the ethical principles of the “Declaration of Helsinki” for medical research on human subjects. All animal experiments were conducted with the approval of the Animal Care and Use Committee of the Shandong Provincial Hospital Affiliated to Shandong First Medical University (Approval Number: 2019–341).
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Gu, X., Sun, X., Yu, Y. et al. MiR-218-5p promotes trophoblast infiltration and inhibits endoplasmic reticulum/oxidative stress by reducing UBE3A-mediated degradation of SATB1. J. Cell Commun. Signal. 17, 993–1008 (2023). https://doi.org/10.1007/s12079-023-00751-0
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DOI: https://doi.org/10.1007/s12079-023-00751-0