Effect and mechanism of microRNA-515-5p in proliferation and apoptosis of trophoblast cells in preeclampsia via manipulating histone deacetylase 2

IF 3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Reproduction and Development Pub Date : 2022-12-29 DOI:10.1002/mrd.23649
Ke Zhang, Hailing Zhang, Shanshan Gao, Caiping Sun, Bing Wang
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Abstract

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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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
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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来源期刊
CiteScore
5.20
自引率
0.00%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Molecular Reproduction and Development takes an integrated, systems-biology approach to understand the dynamic continuum of cellular, reproductive, and developmental processes. This journal fosters dialogue among diverse disciplines through primary research communications and educational forums, with the philosophy that fundamental findings within the life sciences result from a convergence of disciplines. Increasingly, readers of the Journal need to be informed of diverse, yet integrated, topics impinging on their areas of interest. This requires an expansion in thinking towards non-traditional, interdisciplinary experimental design and data analysis.
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