Down‐regulated lncRNA AGAP2‐AS1 contributes to pre‐eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype

Abstract

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 lncR-NAs 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. K E Y W O R D SAGAP2-AS1, FOXP1, JDP2, pre-eclampsia, trophoblastic phenotype

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