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

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.

Drug-eluting intraocular lens with sustained bromfenac release for conquering posterior capsular opacification

“…PCO mainly comes from the proliferation, migration, fibrosis, and EMT of LECs in the lens capsule after stimulation by several growth factors and cytokines [ 43 ]. The development of anterior subcapsular cataract (ASC) and PCO closely relates to the EMT of LECs triggered by a diverse set of stimuli, of which the TGF-β2 growth factor is one of the most [ 44 , 45 ]. Previous studies demonstrated that TGF-β2 played an essential role in the formation of PCO via the canonical TGF-β/Smad signaling pathway, as well as via non-canonical signaling [ 20 , 46 ].…”

LncRNA NEAT1 antagonizes the inhibition of melanoma proliferation, migration, invasion and EMT by Polyphyllin B

“…Long non-coding RNAs (LncRNAs) can regulate a variety of biological functions in the body. Among the nuclear transcription factors, LncRNA NEAT1 has been reported to be involved in the invasion, migration and EMT of a variety of tumor cells, including osteosarcoma cells (Chen et al 2021), lens epithelial cells (Dong 2020), endometrioid adenocarcinoma cells (Li et al 2016) and retinoblastoma cells (Luan et al 2021). These studies demonstrate that NEAT1 promotes cancer progression, migration, invasion and EMT.…”

Knockdown of lncRNA XIST prevents the epithelial-mesenchymal transition of TGF-β2-induced human lens epithelial cells via miR-124/Slug axis

“…It plays a vital role in the activation and promotion of EMT in LECs through the Smads pathway, PI3K/Akt pathway, and other pathways. Besides, TGF-β2 is the primary subtype of the TGF-β family in aqueous humor (Dong, 2020;Zhang et al, 2017). Therefore, TGF-β2induced human lens epithelial cells (HLECs) can be used to simulate the PCO microenvironment (Wang et al, 2019;Zhang et al, 2017).…”