Role of lncRNA NEAT1 mediated by YY1 in the development of diabetic cataract via targeting the microRNA-205-3p/MMP16 axis

Eur Rev Med Pharmacol Sci. 2020 Jun;24(11):5863-5870. doi: 10.26355/eurrev_202006_21478.

Abstract

Objective: We aimed at investigating the possible role and mechanism of NEAT1 in the pathogenesis of diabetic cataract.

Patients and methods: YY1 and NEAT1 expressions in anterior lens capsule collected from diabetic cataract (DC) patients and normal controls were examined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and their correlation was analyzed. The binding site between YY1 and NEAT1 sequences was predicted by JASPAR and detected by Dual-Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. The proliferation and apoptosis of high-glucose-induced cells with NEAT1 knockdown were detected. Potential downstream targets of NEAT1 were predicted by bioinformatics and detected by Dual-Luciferase reporter assay.

Results: YY1 and NEAT1 expressions in the anterior capsule tissue of DC lens were remarkably reduced and positively correlated. Dual-Luciferase reporter assay and ChIP confirmed that YY1 could bind to locus 2 of NEAT1. Knockdown of NEAT1 inhibited proliferation while promoted apoptosis under high glucose conditions. Further mechanism studies revealed that knockdown of NEAT1 could upregulate microRNA-205-3p, and MMP16 was a potential target of miR-205.

Conclusions: The low expression of YY1 induces NEAT1 downregulation, which regulates microRNA-205-3p/MMP16 axis and thus participates in the development of DC.

MeSH terms

  • Apoptosis
  • Cataract / metabolism*
  • Cataract / pathology
  • Cell Proliferation
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Humans
  • Matrix Metalloproteinase 16 / genetics
  • Matrix Metalloproteinase 16 / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Tumor Cells, Cultured
  • YY1 Transcription Factor / genetics
  • YY1 Transcription Factor / metabolism*

Substances

  • MIRN205 microRNA, human
  • MMP16 protein, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • YY1 Transcription Factor
  • YY1 protein, human
  • Matrix Metalloproteinase 16