Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Oct;22(10):e3231.
doi: 10.1002/jgm.3231. Epub 2020 Jun 12.

LINC01121 induced intervertebral disc degeneration via modulating miR-150-5p/MMP16 axis

Xin Chen  1 , Zheng Li  1 , Derong Xu  2 , Shugang Li  1
Affiliations

LINC01121 induced intervertebral disc degeneration via modulating miR-150-5p/MMP16 axis

Xin Chen et al. J Gene Med. 2020 Oct.

Abstract

Background: Growing evidence indicates that Long noncoding RNAs contribute to cell differentiation, invasion, metabolism, proliferation and metastasis. However, the potential role of LINC01121 in progression of intervertebral disc degeneration (IDD) remains unclear.

Methods: LINC01121, matrix metalloprotease (MMP)-16 and miR-150-5p expression was determined by a quantitative-reverse transcriptase-polymerase chain reaction assay. Inflammatory cytokines level was measured by an enzyme-linked immunosorbent assay and cell counting kit-8 analysis was used to assess cell proliferation. MMP-16-specific binding with miR-150-5p was verified with a luciferase reporter assay.

Results: We noted that interleukin (IL)-1β and tumor necrosis factor (TNF)-α treatment enhanced LINC01121 and MMP-16 expression in nucleus pulposus (NP) cells. LINC01121 was higher in IDD specimens compared to that in control specimens. Higher expression of LINC01121 was correlated with disc degeneration degree. Ectopic expression of LINC01121 enhanced cell proliferation and promoted ki-67, MMP-3 and ADAMTS5 expression and also suppressed collagen II expression in NP cells. We observed that overexpression of LINC01121 increased the secretion of three inflammatory cytokines, including IL-6, TNF-α and IL-1β. We found that ectopic expression of LINC01121 decreased the miR-150-5p level in NP cells. Luciferase reporter data confirmed that MMP-16 was one direct target of miR-150-5p. Overexpression of miR-150-5p inhibited MMP-16 level and elevated the expression of LINC01121 enhanced MMP-16 level. We also found that MMP-16 was up-regulated in IDD specimens compared to that in control specimens. Higher expression of MMP-16 was correlated with disc degeneration degree. Interestingly, MMP-16 expression was positively related to LINC01121 in IDD specimens. Finally, overexpression of LINC01121 regulated cell growth, extracellular matrix degradation and inflammatory cytokine secretion via modulating MMP-16.

Conclusions: our data suggested LINC01121 may be a new therapeutic target for IDD.

Keywords: LINC01121; MMP-16; intervertebral disc degeneration; miR-150-5p.

PubMed Disclaimer

References

REFERENCES

    1. Li Z, Shen J, Wu WK, et al. The role of leptin on the organization and expression of cytoskeleton elements in nucleus pulposus cells. Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society. 2013;31:847-857.
    1. Tian Y, Yuan W, Fujita N, et al. Inflammatory cytokines associated with degenerative disc disease control aggrecanase-1 (ADAMTS-4) expression in nucleus pulposus cells through MAPK and NF-kappaB. Am J Pathol. 2013;182:2310-2321.
    1. Seguin CA, Pilliar RM, Madri JA, Kandel RA. TNF-alpha induces MMP2 gelatinase activity and MT1-MMP expression in an in vitro model of nucleus pulposus tissue degeneration. Spine. 2008;33:356-365.
    1. Pockert AJ, Richardson SM, Le Maitre CL, et al. Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration. Arthritis Rheum. 2009;60:482-491.
    1. Li Z, Yu X, Liang J, Wu WKK, Yu J, Shen J. Leptin downregulates aggrecan through the p38-ADAMST pathway in human nucleus pulposus cells. PLoS ONE. 2014;9:e109595.

Publication types

MeSH terms

LinkOut - more resources