microRNA-515-5p通过调控组蛋白去乙酰化酶2在子痫前期滋养细胞增殖和凋亡中的作用及机制

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2022-12-29 DOI:10.1002/mrd.23649
Ke Zhang, Hailing Zhang, Shanshan Gao, Caiping Sun, Bing Wang
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引用次数: 0

摘要

先兆子痫(PE)是指一种始于胎盘的妊娠特异性疾病。差异表达的microRNAs (miRs)是PE的一个特征。本研究试图揭示miR-515-5p在PE中滋养细胞行为中的作用机制。首先,用miR-515-5p模拟物或miR-515-5p抑制剂转染HTR-8/SVneo细胞。然后,通过逆转录-定量聚合酶链反应测定miR-515-5p和组蛋白去乙酰化酶2 (HDAC2)在HTR-8/SVneo细胞中的相对表达水平。在Targetscan上预测miR-515-5p和HDAC2的潜在结合位点,并通过双荧光素酶测定验证它们的结合关系。分别通过细胞计数试剂盒-8、流式细胞术、Transwell和伤口愈合试验评估HTR-8/SVneo细胞的增殖、凋亡、侵袭和迁移。Western blot检测Cleaved caspase-3、Bcl-2、Bax蛋白水平。过表达miR-515-5p抑制HTR-8/SVneo细胞增殖,刺激细胞凋亡,降低Cleaved caspase-3和Bax水平,升高Bcl-2,抑制miR-515-5p后,结果相反。miR-515-5p靶向HDAC2。HDAC2的敲低使miR-515-5p抑制HTR-8/SVneo细胞增殖、侵袭和迁移能力的促进作用及其抗凋亡作用消失。总之,miR-515-5p通过靶向HDAC2影响HTR-8/SVneo细胞的增殖、凋亡、侵袭和迁移。
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Effect and mechanism of microRNA-515-5p in proliferation and apoptosis of trophoblast cells in preeclampsia via manipulating histone deacetylase 2

Preeclampsia (PE) refers to a pregnancy-specific disease that begins with the placenta. Differentially expressed microRNAs (miRs) are a feature of PE. This study tried to elicit the functional mechanism of miR-515-5p in trophoblast cell behaviors in PE. First, HTR-8/SVneo cells were transfected with miR-515-5p mimic or miR-515-5p inhibitor. Then, relative expression levels of miR-515-5p and histone deacetylase 2 (HDAC2) in HTR-8/SVneo cells were determined by reverse transcription-quantitative polymerase chain reaction. The potential binding site of miR-515-5p and HDAC2 was predicted on Targetscan and their binding relationship was verified via dual-luciferase assay. Proliferation, apoptosis, invasion, and migration of HTR-8/SVneo cells were assessed via cell counting kit-8, flow cytometry, Transwell, and wound healing assays, respectively. Protein levels of Cleaved caspase-3, Bcl-2, and Bax were determined via Western blot. Overexpressed miR-515-5p impeded proliferation and stimulated apoptosis of HTR-8/SVneo cells, and decreased levels of Cleaved caspase-3 and Bax and elevated Bcl-2, whilst opposite results were observed after miR-515-5p inhibition. miR-515-5p targeted HDAC2. Knockdown of HDAC2 annulled the promotional action of miR-515-5p inhibition on proliferative, invasive, and migratory abilities and its antiapoptotic action on HTR-8/SVneo cells. In brief, miR-515-5p affected the proliferation, apoptosis, invasion, and migration of HTR-8/SVneo cells by targeting HDAC2.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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