The targeting of DAPK1 with miR-190a-3p promotes autophagy in trophoblast cells

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-01-23 DOI:10.1002/mrd.23724
Qi-qi Luo, Yu Tian, Guang-jin Qu, Kun Huang, Pan-pan Hu, Ying Xue, Bi-feng Hu, Shan-shun Luo
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Abstract

Pre-eclampsia (PE) is a dangerous pathological status that occurs during pregnancy and is a leading reason for both maternal and fetal death. Autophagy is necessary for cellular survival in the face of environmental stress as well as cellular homeostasis and energy management. Aberrant microRNA (miRNA) expression is crucial in the pathophysiology of PE. Although studies have shown that miRNA (miR)-190a-3p function is tissue-specific, the precise involvement of miR-190a-3p in PE has yet to be determined. We discovered that miR-190a-3p was significantly lower and death-associated protein kinase 1 (DAPK1) was significantly higher in PE placental tissues compared to normal tissues, which is consistent with the results in cells. The luciferase analyses demonstrated the target-regulatory relationship between miR-190a-3p and DAPK1. The inhibitory effect of miR-190a-3p on autophagy was reversed by co-transfection of si-DAPK1 and miR-190a-3p inhibitors. Thus, our data indicate that the hypoxia-dependent miR-190a-3p/DAPK1 regulatory pathway is implicated in the development and progression of PE by promoting autophagy in trophoblast cells.

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用 miR-190a-3p 靶向 DAPK1 可促进滋养层细胞的自噬作用
子痫前期(PE)是一种发生在妊娠期的危险病理状态,是导致母体和胎儿死亡的主要原因。自噬是细胞在环境压力下生存以及细胞平衡和能量管理的必要条件。微小核糖核酸(miRNA)表达异常在 PE 的病理生理学中至关重要。尽管研究表明 miRNA(miR)-190a-3p 的功能具有组织特异性,但 miR-190a-3p 在 PE 中的确切参与程度仍有待确定。我们发现,与正常组织相比,PE 胎盘组织中 miR-190a-3p 明显降低,死亡相关蛋白激酶 1(DAPK1)明显升高,这与细胞中的结果一致。荧光素酶分析表明了 miR-190a-3p 和 DAPK1 之间的靶调控关系。同时转染 si-DAPK1 和 miR-190a-3p 抑制剂可逆转 miR-190a-3p 对自噬的抑制作用。因此,我们的数据表明,缺氧依赖的 miR-190a-3p/DAPK1 调控途径通过促进滋养层细胞的自噬,与 PE 的发生和发展有关。
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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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