Long noncoding RNA LINC00958 accelerates the proliferation and matrix degradation of the nucleus pulposus by regulating miR-203/SMAD3

Aging (Albany NY). 2019 Dec 5;11(23):10814-10825. doi: 10.18632/aging.102436. Epub 2019 Dec 5.

Abstract

Emerging evidence suggests that long noncoding RNAs (lncRNAs) play important roles in the development of intervertebral disc degeneration (IDD). LncRNA LINC00958 has recently been shown to play crucial roles in the development of tumors. However, the role of LINC00958 in IDD remains unclear. We showed that the expression of lncRNA LINC00958 was upregulated in degenerative NP samples, and LINC00958 expression increased gradually along with the grade of exacerbation of disc degeneration. Ectopic expression of LINC00958 promoted nucleus pulposus (NP) cell proliferation, inhibited aggrecan and Col II expression and promoted MMP-2 and MMP-13 expression. In addition, we showed that miR-203 expression was downregulated in degenerative NP samples, and miR-203 expression reduced gradually along with the grade of exacerbation of disc degeneration. Moreover, we demonstrated that the expression of miR-203 was inversely related with LINC00958 expression in NP samples. Ectopic expression of miR-203 inhibited NP cell growth and inhibited ECM degradation. Furthermore, we showed that ectopic expression of miR-203 suppressed the luciferase activity of the wild-type LINC00958 3'-UTR but not the mutant LINC00958 3'-UTR. Elevated expression of LINC00958 inhibited the expression of miR-203 and promoted the expression of SMAD3. In addition, we demonstrated that lncRNA LINC00958 exerted its function by targeting miR-203 in the NP cells. These data suggested that dysregulated lncRNA LINC00958 expression might play an important role in the development of IDD.

Keywords: LINC00958; intervertebral disc degeneration; miR-203; nucleus pulposus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Aging
  • Cell Proliferation*
  • Collagen Type II
  • Down-Regulation
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation / physiology
  • Humans
  • Intervertebral Disc Degeneration
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nucleus Pulposus / cytology
  • Nucleus Pulposus / metabolism
  • Nucleus Pulposus / pathology*
  • RNA, Long Noncoding*
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism*
  • Up-Regulation
  • Young Adult

Substances

  • Aggrecans
  • Collagen Type II
  • MIRN203 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SMAD3 protein, human
  • Smad3 Protein
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • MMP2 protein, human
  • Matrix Metalloproteinase 2