miR-101-5p suppresses trophoblast cell migration and invasion via modulating the DUSP6-ERK1/2 axis in preeclampsia
miR-101-5p suppresses trophoblast cell migration and invasion via modulating the DUSP6-ERK1/2 axis in preeclampsia
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DOI：
10.1007/s10815-023-02846-4
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发表时间：
2023-06
影响因子：
3.1
通讯作者：
Jiacheng Xu;Jie-Fu Wang;Miaomiao Chen;Bingdi Chao;Jie He;Yuxiang Bai;Xiaofang Luo;Hongli Liu;Lumei Xie;Yuelan Tao;H. Qi;Xin Luo
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文献类型：
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作者：
Jiacheng Xu;Jie-Fu Wang;Miaomiao Chen;Bingdi Chao;Jie He;Yuxiang Bai;Xiaofang Luo;Hongli Liu;Lumei Xie;Yuelan Tao;H. Qi;Xin Luo
目的滋养细胞行为失调导致胎盘缺陷被认为是子痫前期（PE）的主要原因。在PE胎盘组织中观察到异常的miRNA表达谱，表明miRNA在PE发育中的重要作用。本研究旨在探讨miR-101-5p在PE胎盘组织中的表达及其生物学功能。方法采用实时荧光定量PCR （qRT-PCR）检测miR-101-5p在胎盘组织中的表达。采用荧光原位杂交(FISH)-免疫荧光（IF）双标记法检测miR-101-5p在足月胎盘组织和蜕膜组织中的定位。研究miR-101-5p对HTR8/SVneo滋养细胞迁移、侵袭、增殖和凋亡的影响。利用在线数据库结合转录组学鉴定miR-101-5p的潜在靶基因和相关通路。最后，通过qRT-PCT、WB、双荧光素酶报告基因实验和救援实验验证miR-101-5p与靶基因的相互作用。结果研究发现，miR-101-5p在PE胎盘组织中与正常对照组相比表达上调，主要位于胎盘和蜕膜组织的各种滋养细胞亚型中。过表达miR-101-5p可抑制HTR8/SVneo细胞的迁移和侵袭。DUSP6被确定为miR-101-5p的潜在下游靶点。在HTR8/SVneo细胞中，miR-101-5p的表达与DUSP6的表达呈负相关，并且miR-101-5p直接结合到DUSP6的3 ' UTR区。在miR-101-5p过表达的情况下，DUSP6上调挽救了HTR8/SVneo细胞的迁移和侵袭能力。此外，miR-101-5p下调DUSP6，导致ERK1/2磷酸化增强。结论本研究揭示miR-101-5p通过调控DUSP6-ERK1/2轴抑制HTR8/SVneo细胞的迁移和侵袭，为PE的发病提供了新的分子机制。
PurposeDysregulated behaviors of trophoblast cells leading to defective placentation are considered the main cause of preeclampsia (PE). Abnormal miRNA expression profiles have been observed in PE placental tissue, indicating the significant role of miRNAs in PE development. This study aimed to investigate the expression of miR-101-5p in PE placental tissue and its biological functions.MethodsThe expression of miR-101-5p in placental tissue was detected by quantitative real-time PCR (qRT-PCR). The localization of miR-101-5p in term placental tissue and decidual tissue was determined by the fluorescence in situ hybridization (FISH)-immunofluorescence (IF) double labeling assay. The effect of miR-101-5p on the migration, invasion, proliferation, and apoptosis of the HTR8/SVneo trophoblast cells was investigated. Online databases combined with transcriptomics were used to identify potential target genes and related pathways of miR-101-5p. Finally, the interaction between miR-101-5p and the target gene was verified by qRT-PCT, WB, dual-luciferase reporter assay, and rescue experiments.ResultsThe study found that miR-101-5p was upregulated in PE placental tissue compared to normal controls and was mainly located in various trophoblast cell subtypes in placental and decidual tissues. Overexpression of miR-101-5p impaired the migration and invasion of HTR8/SVneo cells. DUSP6 was identified as a potential downstream target of miR-101-5p. The expression of miR-101-5p was negatively correlated with DUSP6 expression in HTR8/SVneo cells, and miR-101-5p directly bound to the 3′ UTR region of DUSP6. DUSP6 upregulation rescued the migratory and invasive abilities of HTR8/SVneo cells in the presence of miR-101-5p overexpression. Additionally, miR-101-5p downregulated DUSP6, resulting in enhanced ERK1/2 phosphorylation.ConclusionThis study revealed that miR-101-5p inhibits the migration and invasion of HTR8/SVneo cells by regulating the DUSP6-ERK1/2 axis, providing a new molecular mechanism for the pathogenesis of PE.