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微小 RNA-30a-3p 在子痫前期患者的胎盘中过度表达,并通过对 IGF-1 的影响影响滋养细胞的侵袭和凋亡。

MicroRNA-30a-3p is overexpressed in the placentas of patients with preeclampsia and affects trophoblast invasion and apoptosis by its effects on IGF-1.

机构信息

Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China; Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong, China.

Department of Orthopedics, Hainan Branch of PLA General Hospital, Sanya, China.

出版信息

Am J Obstet Gynecol. 2018 Feb;218(2):249.e1-249.e12. doi: 10.1016/j.ajog.2017.11.568. Epub 2017 Nov 16.

Abstract

OBJECTIVE

Preeclampsia (PE) affects many women globally and remains a primary cause of neonatal and maternal morbidity and mortality. Aberrant placental microRNA (miRNA) expression might be associated with PE. Previously, 33 PE-related miRNAs, 11 up-regulated and 23 down-regulated, were detected in placentas of women with severe PE when compared with those of normal patients. One of the most up-regulated miRNAs in PE is miR-30a-3p. The predicted target of it is insulin-like growth factor 1 (IGF-1), which has been reported to have a relatively low expression level in PE patients. This study was conducted to determine the aberrant increased of miR-30a-3p in the placentas of women with preeclampsia and to elucidate the target and function of it in trophoblast cells.

STUDY DESIGN

miR-30a-3p expression in placenta tissues was compared between women with preeclampsia (n = 25) and normal pregnant women (n = 20). The miRNA target was studied by in silico and functional assay. The effects of the miRNA were verified by apoptosis assay and invasion assay in the trophoblast cell line.

RESULTS

miR-30a-3p was increased significantly in the placenta of women with preeclampsia when compared to those with normal pregnancies. Luciferase assay confirmed direct regulation of miR-30a-3p on the expression of IGF-1. Forced expression of miR-30a-3p suppressed IGF-1 protein expression in the HTR-8/SVneo cells. The functional assay suggests that the over-expression of miR-30a-3p alter the invasive capacity of JEG-3 cells and induce the apoptosis of HTR-8/SVneo cells (Figure).

CONCLUSION

Expression of miR-30a-3p was significantly increased in the placentas of patients with preeclampsia. miR-30a-3p might be involved in the pathogenesis of preeclampsia by targeting IGF-1 and regulating the invasion and apoptosis of trophoblast cells.

摘要

目的

子痫前期(PE)影响全球许多女性,仍是导致新生儿和孕产妇发病率和死亡率的主要原因。胎盘微小 RNA(miRNA)表达异常可能与 PE 有关。此前,在与正常患者的胎盘相比时,在患有严重 PE 的女性的胎盘组织中检测到 33 个与 PE 相关的 miRNA,其中 11 个上调,23 个下调。PE 中上调最明显的 miRNA 之一是 miR-30a-3p。其预测靶标是胰岛素样生长因子 1(IGF-1),据报道,IGF-1 在 PE 患者中的表达水平相对较低。本研究旨在确定 miR-30a-3p 在子痫前期患者胎盘组织中的异常增加,并阐明其在滋养细胞中的靶标和功能。

研究设计

比较 25 例子痫前期妇女和 20 例正常妊娠妇女胎盘组织中的 miR-30a-3p 表达。通过计算机模拟和功能测定研究 miRNA 靶标。通过在滋养细胞系中的凋亡测定和侵袭测定验证 miRNA 的作用。

结果

与正常妊娠妇女相比,子痫前期妇女胎盘组织中的 miR-30a-3p 显著增加。荧光素酶测定证实 miR-30a-3p 直接调节 IGF-1 的表达。miR-30a-3p 的强制表达抑制了 HTR-8/SVneo 细胞中 IGF-1 蛋白的表达。功能测定表明,miR-30a-3p 的过表达改变了 JEG-3 细胞的侵袭能力,并诱导 HTR-8/SVneo 细胞的凋亡(图)。

结论

miR-30a-3p 在子痫前期患者的胎盘组织中表达显著增加。miR-30a-3p 可能通过靶向 IGF-1 并调节滋养细胞的侵袭和凋亡而参与子痫前期的发病机制。

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