LncRNA NR_003923 promotes cell proliferation, migration, fibrosis, and autophagy via the miR-760/miR-215-3p/IL22RA1 axis in human Tenon's capsule fibroblasts

Cell Death Dis. 2019 Aug 7;10(8):594. doi: 10.1038/s41419-019-1829-1.

Abstract

Noncoding RNAs (ncRNAs), including long ncRNAs (lncRNA) have manifested an important role in the pathophysiology of many diseases. Glaucoma is a primary cause of irreversible blindness worldwide. However, the involvement of lncRNAs in glaucoma remains largely unknown. Here, we performed the lncRNA expression assay based on clinical tissues and identified a specific functional lncRNA, NR_003923, and investigated its potential role in glaucoma. Knockdown of NR_003923 in human Tenon's capsule fibroblast cells (HTFs) inhibited TGF-β-induced cell migration, proliferation, fibrosis, and autophagy. The dual luciferase reporter assay confirmed that miR-760 and miR-215-3p interacted with NR_003923. miR-760 and miR-215-3p inhibitor reversed the effects of NR_003923 and TGF-β-induced cell apoptosis. Moreover, the expression of miR-760 and miR-215-3p was decreased in glaucoma comparing with control. Furthermore, through microarray we found IL22RA1 was increased in glaucoma and both of miR-760 and miR-215-3p bound to the 3' UTR of IL22RA1. Overexpression of IL22RA1 enhanced HTFs migration and proliferation, while miR-760 and miR-215-3p mimics reversed these promotive biological roles induced by IL22RA1. In conclusion, NR_003923 and IL22RA1 might contribute to glaucoma progression and be a novel and potential biomarkers and therapeutic targets for glaucoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibrosis / genetics
  • Fibrosis / pathology
  • Gene Expression Regulation / genetics
  • Gene Knockdown Techniques
  • Glaucoma / genetics*
  • Glaucoma / pathology
  • Humans
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Receptors, Interleukin / genetics*
  • Tenon Capsule / growth & development
  • Tenon Capsule / metabolism
  • Tenon Capsule / pathology

Substances

  • MIRN215 microRNA, human
  • MIRN760 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Receptors, Interleukin
  • interleukin-22 receptor