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Down‐regulated lncRNA AGAP2‐AS1 contributes to pre‐eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2020
- Publisher :
- John Wiley and Sons Inc., 2020.
-
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 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.
- Subjects :
- 0301 basic medicine
Adult
Placenta
Cell Culture Techniques
Context (language use)
FOXP1
Biology
03 medical and health sciences
JDP2
0302 clinical medicine
Pre-Eclampsia
Pregnancy
AGAP2‐AS1
Gene silencing
Humans
Cell Proliferation
Gene knockdown
Cell growth
Competing endogenous RNA
Forkhead Transcription Factors
Cell Biology
Original Articles
Phenotype
pre‐eclampsia
Trophoblasts
Repressor Proteins
MicroRNAs
030104 developmental biology
Gene Expression Regulation
030220 oncology & carcinogenesis
embryonic structures
trophoblastic phenotype
Jun dimerization protein
biology.protein
Cancer research
Molecular Medicine
Original Article
Female
RNA, Long Noncoding
Subjects
Details
- Language :
- English
- ISSN :
- 15824934 and 15821838
- Volume :
- 24
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....f86581cba60c99add89b22adaade2200