microRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells
microRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells
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microRNA-29b 通过影响滋养层细胞的凋亡、侵袭和血管生成而导致先兆子痫
DOI：
10.1042/cs20120121
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发表时间：
2013-01-01
期刊：
影响因子：
6
通讯作者：
Hou, Yayi
中科院分区：
文献类型：
--
作者：
Li, Pengfei;Guo, Wei;Hou, Yayi
PE（先兆子痫）是一种妊娠特异性疾病，其特征在于滋养层细胞死亡增加和滋养层侵袭缺陷以及滋养层介导的螺旋动脉重塑减少。本研究旨在确定miR-29 b（nmicroRNA-29 b）在滋养层细胞中的功能及其在PE发病机制中的潜在作用。使用基于计算机的程序（包括Targetscan、Pictar和miRBase）进行miR-29 b靶基因的预测。利用基因本体论（GO）对这些目的基因的功能进行了进一步的分析。分别采用流式细胞术和Matrigel法检测miR-29 b对HTR-8/SVneo、BeWo和HUVEC细胞凋亡、侵袭和血管生成的影响。我们发现miR-29 b可诱导滋养层细胞凋亡，并抑制滋养层细胞的侵袭和血管生成。进一步的研究证实，miR-29 b通过直接结合其3 '-UTR（非翻译区）来调节MCL 1（髓细胞白血病序列1）、MMP 2（编码基质金属蛋白酶2）、VEGFA（血管内皮生长因子A）和ITGB 1（整合素β 1）基因的表达。此外，我们发现，在PE受试者中，miR-29 b与其靶基因之间存在负相关性。综上所述，这些发现支持miR-29 b在滋养层细胞的侵袭、凋亡和血管生成中的新作用，并且miR-29 b可能成为PE的新的潜在治疗靶点。
PE (pre-eclampsia), a pregnancy-specific disorder, is characterized by increased trophoblast cell death and deficient trophoblast invasion and reduced trophoblast-mediated remodelling of spiral arteries. The present study was performed to determine the function of miR-29b (nnicroRNA-29b) in trophoblast cells and its underlying role in the pathogenesis of PE. The prediction of miR-29b target genes was performed using computer-based programs, including Targetscan, Pictar and miRBase. The function of these target genes was analysed further by gene ontology (GO). The effects of miR-29b on apoptosis, and invasion and angiogenesis of trophoblast cell lines (HTR-8/SVneo, BeWo and JAR) were examined by flow cytometry and Matrigel assay respectively. We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin beta 1) genes by directly binding to their 3'-UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. Taken together, these findings support a novel role for miR-29b in invasion, apoptosis and angiogenesis of trophoblast cells, and miR-29b may become a new potential therapeutic target for PE.