MiR-218-5p promotes trophoblast infiltration and inhibits endoplasmic reticulum/oxidative stress by reducing UBE3A-mediated degradation of SATB1

• Published in: Journal of cell communication and signaling Vol. 17; no. 3; pp. 993 - 1008
• Main Authors: Gu, Xiao, Sun, Xiaomei, Yu, Yanling, Li, Lei
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.09.2023; John Wiley & Sons, Inc
• Subjects: Amino acid sequence; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell migration; Degradation; Endoplasmic reticulum; Gelatinase A; Hypoxia-inducible factor 1a; Immunoprecipitation; Infiltration; Intracellular; Life Sciences; MiR‐218‐5p; Oxidation; Oxidative stress; Placenta; Pre-eclampsia; Reactive oxygen species; Research Article; SATB1; Tissue inhibitor of metalloproteinase 1; Transfection; Trophoblast infiltration; UBE3A; Ubiquitin; Ubiquitin-protein ligase; Ubiquitination; Western blotting; Ubiquitination; UBE3A; Trophoblast infiltration; SATB1; MiR-218-5p
• ISSN: 1873-9601; 1873-961X
• DOI: 10.1007/s12079-023-00751-0

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.