LINC00969 promotes the degeneration of intervertebral disk by sponging miR-335-3p and regulating NLRP3 inflammasome activation

IUBMB Life. 2019 May;71(5):611-618. doi: 10.1002/iub.1989. Epub 2018 Dec 28.

Abstract

Long noncoding RNAs (LncRNAs) may serve as miRNA sponges to regulate the expressions of miRNA target genes. LncRNA LINC00969 has been indicated to be upregulated in intervertebral disk degeneration. However, the regulatory mechanism of LINC00969 in intervertebral disk degeneration progression remains unclear. Differently expressed LINC00969, miR-335-3p, and thioredoxin-interacting protein (TXNIP) were determined in nucleus pulposus (NP) tissues and cells isolated from patients with intervertebral disk degeneration. The interaction between LINC00969, miR-335-3p, and TXNIP was also assessed. In this study, we demonstrated that LINC00969 was highly expressed, whereas miR-335-3p was aberrantly downregulated in NP tissues and cells of intervertebral disk degeneration patients. In addition, our results suggested that LINC00969 enhanced NP cell apoptosis. More importantly, LINC00969 was identified to function as a competitive endogenous RNA (ceRNA) for miR-335-3p to positively regulate TXNIP expression in vitro. Our study provided evidence for the cross-talk between LINC00969, miR-335-3p, and TXNIP, shedding light on the therapy for intervertebral disk degeneration. © 2018 IUBMB Life, 71(5):611-618, 2019.

Keywords: LINC00969; NOD-like receptor protein 3; intervertebral disk degeneration; miR-335-3p; thioredoxin-interacting protein.

MeSH terms

  • Case-Control Studies
  • Gene Expression Regulation*
  • Humans
  • Inflammasomes*
  • Intervertebral Disc Degeneration / genetics
  • Intervertebral Disc Degeneration / metabolism
  • Intervertebral Disc Degeneration / pathology*
  • MicroRNAs / genetics*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology*

Substances

  • Inflammasomes
  • LINC00978 long noncoding RNA, human
  • MIRN335 microRNA, human
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • RNA, Long Noncoding