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Long Noncoding RNA NEAT1 Regulates TGF-β2-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through the miR-34a/Snail1 and miR-204/Zeb1 Pathways
- Source :
- BioMed Research International, Vol 2020 (2020)
- Publication Year :
- 2020
- Publisher :
- Hindawi Limited, 2020.
-
Abstract
- The aim of this study was to explore whether the long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1)/miR-34a/Snail1 and NEAT1/miR-204/Zeb1 pathways are involved in epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). Primary human LECs (HLECs) were separated and cultured. Our results identified that TGF-β2 induces NEAT1 overexpression in a dose-dependent manner and a time-dependent manner. Additionally, TGF-β2 induced downregulation of E-cadherin and upregulation of fibronectin in primary HLECs through a NEAT1-dependent mechanism. Microarray analysis showed that NEAT1 overexpression inhibited the miR-34a and miR-204 levels in the LECs. The expression of miR-34a and miR-204 was decreased, and the levels of Snail1 and Zeb1 were elevated in human posterior capsule opacification- (PCO-) attached LECs and the LECs obtained from anterior subcapsular cataract (ASC) by quantitative RT-PCR (qRT-PCR). Mechanistic studies revealed that NEAT1 negatively regulates miR-34a or miR-204, and miR-34a or miR-204 directly targets Snail1 or Zeb1 by luciferase assay and RNA-binding protein immunoprecipitation assay, respectively. Overall, the NEAT1/miR-34a/Snail1 and NEAT1/miR-204/Zeb1 pathways are involved in TGF-β2-induced EMT of HLECs. In summary, TGF-β2 induces NEAT1 overexpression, which in turn suggests that NEAT1 acts as a ceRNA targeting Snail1 or Zeb1 by binding miR-34a or miR-204, and promotes the progression of EMT of LECs.
- Subjects :
- 0301 basic medicine
Article Subject
General Immunology and Microbiology
Competing endogenous RNA
Chemistry
Immunoprecipitation
Microarray analysis techniques
Paraspeckle
General Medicine
General Biochemistry, Genetics and Molecular Biology
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Downregulation and upregulation
030221 ophthalmology & optometry
Medicine
Luciferase
Epithelial–mesenchymal transition
Transforming growth factor
Subjects
Details
- Language :
- English
- ISSN :
- 23146141 and 23146133
- Volume :
- 2020
- Database :
- OpenAIRE
- Journal :
- BioMed Research International
- Accession number :
- edsair.doi.dedup.....44ffab84c201c209e6316fa00a51a904