Down-regulated lncRNA AGAP2-AS1 contributes to pre-eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype
Down-regulated lncRNA AGAP2-AS1 contributes to pre-eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype
复制标题
下调的lncRNA AGAP2-AS1作为JDP2的竞争性内源RNA通过损害滋养层表型而导致先兆子痫
DOI：
10.1111/jcmm.15113
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发表时间：
2020
影响因子：
5.3
通讯作者：
Sun Lizhou
中科院分区：
文献类型：
--
作者：
Xu Yetao;Xia Xi;Jiang Ying;Wu Dan;Wang Sailan;Fu Shilong;Yang Nana;Zhang Yuanyuan;Sun Lizhou
Recently, growing evidence has shown that aberrant long non‐coding RNA (lncRNA) expression in conjunction with an impaired trophoblastic phenotype could implicate the pathological process of pre‐eclampsia (PE). However, only a small portion of lncRNAs has been characterized with regard to the function and molecular mechanisms involved in PE. There are still gaps in the available knowledge; as a result, there are currently only a few applicable treatments for PE in the context of lncRNA. Here, we found that lncRNA AGAP2‐AS1 is abnormally down‐regulated in severe PE placenta tissues. Using human trophoblasts, we established that AGAP2‐AS1 knockdown could inhibit trophoblasts proliferation and invasion and promote cell apoptosis. Further, we showed that overexpression of AGAP2‐AS1 substantially stimulated the development of the trophoblastic phenotype. Through high‐throughput sequencing analysis, we demonstrated that silencing of AGAP2‐AS1 favourably regulated various genes which are relevant to trophoblastic growth and invasion. Mechanistically, AGAP2‐AS1 promoted the suppressor protein, Jun dimerization protein 2 (JDP2), by sponging miR‐574‐5p. Resultantly, further impairment of the trophoblastic phenotype was achieved by way of inhibiting cell growth, apoptosis and invasion. We also determined that the expression of AGAP2‐AS1 could be mediated by FOXP1. Our results showed that the down‐regulated expression of lncRNA AGAP2‐AS1 might serve as a key suppressor in PE via inhibition of JDP2 at the post‐transcriptional level by competing for miR‐574; thus, this presents a novel therapeutic strategy for PE.
