LncRNA PSMA3-AS1 promotes preterm delivery by inducing ferroptosis via miR-224-3p/Nrf2 axis.
Cell Mol Biol (Noisy-le-grand)
; 69(13): 270-278, 2023 Dec 10.
Article
em En
| MEDLINE
| ID: mdl-38158666
ABSTRACT
Long non-coding RNAs (lncRNAs) have a vital potential in premature delivery. This research was intended to explore PSMA3-AS1's role in premature delivery as well as its possible molecular mechanism. We enrolled 100 premature delivery patients and 100 term patients. Fetal membranes were collected. RT-qPCR was adopted for evaluating PSMA3-AS1, miRNA-224-3p, along with Nrf2 expression. Cell function experiments were implemented to clarify PSMA3-AS1 functions in human trophoblast HTR-8/SVneo cells. Rescue together with mechanistic experiments were implemented for assessing the regulatory function and interaction between miR-224-3p and PSMA3-AS1 or Nrf2 axis in human trophoblast cells. The results uncovered that PSMA3-AS1 level presented downregulation in the fetal membrane tissues and human trophoblast cells. Overexpressed PSMA3-AS1 enhanced cell proliferation but suppressed ferroptosis in human trophoblast cells. Besides, PSMA3-AS1 elevation also attenuated the LPS-induced inflammatory response and restored the LPS-induced upregulation of 20α-HSD and downregulation of progesterone (P4). Mechanistically, miR-224-3p could bind to PSMA3-AS1 and present upregulation in fetal membranes and human trophoblast cells. Notably, overexpressed miR-224-3p offset the influences of PSMA3-AS1 on human trophoblast cell proliferation and ferroptosis. Furthermore, Nrf2 was targeted by miR-224-3p. Downregulated Nrf2 offset the influences of the miR-224-3p inhibitor and induced HTR-8/SVneo dysfunction. Additionally, Nrf2 transcriptionally activated PSMA3-AS1 and GPX4. In conclusion, PSMA3-AS1 expression is low during premature delivery and overexpressing PSMA3-AS1 promotes proliferation and suppresses ferroptosis of human trophoblast cells by interacting with miR-224-3p to downregulate Nrf2. Therefore, enhancing PSMA3-AS1 expression may be a promising therapeutic strategy to prevent premature delivery.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Nascimento Prematuro
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RNA Longo não Codificante
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Ferroptose
Limite:
Female
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Humans
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Newborn
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Pregnancy
Idioma:
En
Revista:
Cell Mol Biol (Noisy-le-grand)
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China