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LncRNA MALAT1 Knockdown Alleviates Fibrogenic Response in Human Endometrial Stromal Cells Via the miR-22-3p/TGFβR1/Smad2/3 Pathway.

LncRNA MALAT1 Knockdown Alleviates Fibrogenic Response in Human Endometrial Stromal Cells Via the miR-22-3p/TGFβR1/Smad2/3 Pathway.

Authors :
Zhu, Zhengyan
Huang, Yu
Song, Yu
Lu, Jingquan
Hu, Lina
Chen, Xuemei
Source :
Cell Biochemistry & Biophysics; Dec2024, Vol. 82 Issue 4, p3573-3584, 12p
Publication Year :
2024

Abstract

Intrauterine adhesion (IUA) resulting from irreversible fibrotic repair of endometrium is the main cause of secondary infertility in women, and current therapeutic approaches to IUA are limited. Increasing evidence has suggested the important role of competitive endogenous RNA (ceRNA) in IUA pathologies. This study aimed to investigate the long noncoding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-associated ceRNA in IUA development. We harvested endometrial tissues from patients with or without IUA and extracted endometrial stromal cells (ESCs) from normal endometrial tissues. Transforming growth factor β1 (TGF-β1) was used to induce fibrosis in ESCs. The expression of transforming growth factor β receptor 1 (TGFβR1), α-smooth muscle actin, phosphorylated suppressor of mother against decapentaplegic (p-Smad)2/3, collagen type I alpha 1, MALAT1, and microRNA (miR)-22-3p in endometrial tissues and ESCs was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) or western blotting. Pearson's correlation analysis was conducted to assess the correlation between miR-22-3p expression or TGFβR1 and MALAT1 expression in endometrial tissues. The expression of TGFβR1 in ESCs was also evaluated by immunofluorescence staining. The location of MALAT1 was examined by fluorescence in situ hybridization. Luciferase reporter assays were performed to verify the binding relationship between MALAT1 or TGFβR1 and miR-22-3p. Cell viability was assessed via cell counting kit-8 assays. Our findings revealed that lncRNA MALAT1 and TGFβR1 were upregulated while miR-22-3p was downregulated in IUA endometrial tissues or TGF-β1-stimulated ESCs, and lncRNA MALAT1 expression was negatively correlated with miR-22-3p expression while being positively correlated with TGFβR1 expression in IUA endometrial tissues. Additionally, lncRNA MALAT1 was mainly located in the cytoplasm of ESCs and directly targeted miR-22-3p to regulate TGFβR1 expression. Moreover, knockdown of lncRNA MALAT1 exerted anti-fibrotic effects on ESCs by targeting miR-22-3p, and miR-22-3p overexpression inhibited the fibrosis of ESCs by binding to TGFβR1 3'untranslated region. Collectively, lncRNA MALAT1 promotes endometrial fibrosis by sponging miR-22-3p to regulate TGFβR1 and Smad2/3, and inhibition of MALAT1 may represent a promising therapeutic option for suppressing endometrial fibrosis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10859195
Volume :
82
Issue :
4
Database :
Complementary Index
Journal :
Cell Biochemistry & Biophysics
Publication Type :
Academic Journal
Accession number :
180991027
Full Text :
https://doi.org/10.1007/s12013-024-01445-z