Open Access

Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR‑185‑5p and matrix metalloproteinase 2

  • Authors:
    • Wei Guo
    • Bin Zhang
    • Chao Sun
    • Hui‑Quan Duan
    • Wei‑Xiao Liu
    • Kun Mu
    • Ling Zhao
    • Hao‑Ran Li
    • Zhan‑Yin Dong
    • Qing Cui
  • View Affiliations

  • Published online on: May 29, 2020     https://doi.org/10.3892/ijmm.2020.4621
  • Pages: 621-632
  • Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intervertebral disc degeneration (IDD) is an important cause of lower back pain, although the underlying mechanisms remain poorly understood. The present study aimed to examine the role of a circular RNA derived from tissue inhibitor of metallopeptidases 2 (circ‑TIMP2) in degenerative nucleus pulposus (NP) tissues, and to validate its function in cultured human NP cells. Overexpression of miR‑185‑5p in NP cells markedly inhibited the enhanced extracellular matrix (ECM) catabolism induced by tumor necrosis factor‑α (TNF‑α) and interleukin‑1β (IL‑1β) treatment. Bioinformatics analysis demonstrated that matrix metalloproteinase 2 (MMP2) was a potential target of miR‑185‑5p. MMP2 protein expression levels were increased following treatment with TNF‑α and IL‑1β in NP cells compared with those in untreated cells, and this effect was attenuated by transfection with miR‑185‑5p. Compared with normal NP tissues, IDD samples exhibited higher circ‑TIMP2 expression levels. In addition, overexpression of circ‑TIMP2 promoted ECM catabolism and suppressed ECM anabolism. Furthermore, circ‑TIMP2 sequestered miR‑185‑5p, which may potentially upregulate the target genes associated with ECM degradation. In conclusion, the results of the present study revealed that circ‑TIMP2 promoted TNF‑α‑ and IL‑1β‑induced NP cell imbalance between ECM anabolism and catabolism via miR‑185‑5p‑MMP2 signaling. These findings provide a potential therapeutic option for the treatment of IDD.
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August-2020
Volume 46 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos
Guo W, Zhang B, Sun C, Duan H, Liu W, Mu K, et al: Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR‑185‑5p and matrix metalloproteinase 2. Int J Mol Med 46: 621-632, 2020
APA
Guo, W., Zhang, B., Sun, C., Duan, H., Liu, W., Mu, K. ... Cui, Q. (2020). Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR‑185‑5p and matrix metalloproteinase 2. International Journal of Molecular Medicine, 46, 621-632. https://doi.org/10.3892/ijmm.2020.4621
MLA
Guo, W., Zhang, B., Sun, C., Duan, H., Liu, W., Mu, K., Zhao, L., Li, H., Dong, Z., Cui, Q."Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR‑185‑5p and matrix metalloproteinase 2". International Journal of Molecular Medicine 46.2 (2020): 621-632.
Chicago
Guo, W., Zhang, B., Sun, C., Duan, H., Liu, W., Mu, K., Zhao, L., Li, H., Dong, Z., Cui, Q."Circular RNA derived from TIMP2 functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR‑185‑5p and matrix metalloproteinase 2". International Journal of Molecular Medicine 46, no. 2 (2020): 621-632. https://doi.org/10.3892/ijmm.2020.4621