Long Non-Coding RNA MALAT1 Mediates Transforming Growth Factor Beta1-Induced Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells

PLoS One. 2016 Mar 28;11(3):e0152687. doi: 10.1371/journal.pone.0152687. eCollection 2016.

Abstract

Purpose: To study the role of long non-coding RNA (lncRNA) MALAT1 in transforming growth factor beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells.

Methods: ARPE-19 cells were cultured and exposed to TGF-β1. The EMT of APRE-19 cells is confirmed by morphological change, as well as the increased expression of alpha-smooth muscle actin (αSMA) and fibronectin, and the down-regulation of E-cadherin and Zona occludin-1(ZO-1) at both mRNA and protein levels. The expression of lncRNA MALAT1 in RPE cells were detected by quantitative real-time PCR. Knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). The effect of inhibition of MALAT1 on EMT, migration, proliferation, and TGFβ signalings were observed. MALAT1 expression was also detected in primary RPE cells incubated with proliferative vitreoretinopathy (PVR) vitreous samples.

Results: The expression of MALAT1 is significantly increased in RPE cells incubated with TGFβ1. MALAT1 silencing attenuates TGFβ1-induced EMT, migration, and proliferation of RPE cells, at least partially through activating Smad2/3 signaling. MALAT1 is also significantly increased in primary RPE cells incubated with PVR vitreous samples.

Conclusion: LncRNA MALAT1 is involved in TGFβ1-induced EMT of human RPE cells and provides new understandings for the pathogenesis of PVR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cadherins / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Fibronectins / metabolism
  • Humans
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism
  • Signal Transduction / drug effects
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / pharmacology*
  • Up-Regulation / drug effects
  • Vitreoretinopathy, Proliferative / metabolism
  • Vitreoretinopathy, Proliferative / pathology
  • Zonula Occludens-1 Protein / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Cadherins
  • Fibronectins
  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Smad2 Protein
  • Smad3 Protein
  • TJP1 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta1
  • Zonula Occludens-1 Protein

Grants and funding

This work was funded by National Natural Science Foundation of China (No. 81300772(HL), 81500727(ML) and No. 81271029(FW)) http://www.nsfc.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.