Long Noncoding RNA NEAT1 Regulates TGF-β2-Induced Epithelial-Mesenchymal Transition of Lens Epithelial Cells through the miR-34aSnail1 and miR-204Zeb1 Pathways

الملخص EN

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.