LncRNA LINC00324 is upregulated in intervertebral disk degeneration and upregulates FasL in nucleus pulposus cells

Abstract

Background

It has been reported that long intergenic non-protein-coding RNA 324 (LINC00324) promotes liver cancer by upregulating Fas ligand (FasL), which is a major player in intervertebral disk degeneration (IDD), indicating the involvement of LINC00324 in IDD. This study was carried out to investigate the interaction between LINC00324 and FasL in IDD.

Methods

Plasma samples were collected from both IDD (n = 60) and healthy controls (n = 60). The expression of LINC00324 and FasL in plasma was determined by RT-qPCR. The interactions between LINC00324 and FasL in nucleus pulposus (NP) cells were analyzed by overexpression experiments.

Results

LINC00324 and FasL were upregulated in IDD patients, and they were positively correlated. After treatment, the expression levels of FasL and LINC00324 were significantly decreased. In NP cells, overexpression of LINC00324 increased the expression of FasL at both mRNA and protein levels, while overexpression of FasL did not affect the expression of LINC00324.

Conclusion

LINC00324 may upregulate FasL in IDD to promote disease progression.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. 1.

    Kaiser J, Allaire B, Fein PM et al (2018) Correspondence between bone mineral density and intervertebral disc degeneration across age and sex. Arch Osteoporos 13(1):123

    Article  Google Scholar 

  2. 2.

    Teraguchi M, Yoshimura N, Hashizume H et al (2017) Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study. Osteoarthr Cartil 25(7):1122–1131

    CAS  Article  Google Scholar 

  3. 3.

    Leimer EM, Gayoso MG, Jing L et al (2019) Behavioral compensations and neuronal remodeling in a rodent model of chronic intervertebral disc degeneration. Sci Rep 9(1):3759

    Article  Google Scholar 

  4. 4.

    Yang T, Li R, Liang N et al (2020) The application of key feature extraction algorithm based on Gabor wavelet transformation in the diagnosis of lumbar intervertebral disc degenerative changes. PLoS One 15(2):e0227894

    CAS  Article  Google Scholar 

  5. 5.

    Sun Z, Liu B, Luo ZJ (2020) The immune privilege of the intervertebral disc: implications for intervertebral disc degeneration treatment. Int J Med Sci 17(5):685–692

    CAS  Article  Google Scholar 

  6. 6.

    van Uden S, Silva-Correia J, Oliveira JM et al (2017) Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities. Biomater Res 21(1):22

    Article  Google Scholar 

  7. 7.

    Wang F, Cai F, Shi R et al (2016) Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration. Osteoarthr Cartil 24(3):398–408

    CAS  Article  Google Scholar 

  8. 8.

    Kepler CK, Ponnappan RK, Tannoury CA et al (2013) The molecular basis of intervertebral disc degeneration. Spine J 13(3):318–330

    Article  Google Scholar 

  9. 9.

    Sampara P, Banala RR, Vemuri SK et al (2018) Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review. Gene Ther 25(2):67–82

    CAS  Article  Google Scholar 

  10. 10.

    Zhang F, Zhao X, Shen H et al (2016) Molecular mechanisms of cell death in intervertebral disc degeneration. Int J Mol Med 37(6):1439–1448

    CAS  Article  Google Scholar 

  11. 11.

    Cui S, Liu Z, Tang B et al (2020) LncRNA MAGI2-AS3 is down-regulated in intervertebral disc degeneration and participates in the regulation of FasL expression in nucleus pulposus cells. BMC Musculoskelet Disord 21(1):149

    CAS  Article  Google Scholar 

  12. 12.

    Gao J, Dai C, Yu X et al (2019) Long non-coding RNA LINC00324 exerts pro-tumorigenic effects on liver cancer stem cells by up-regulating Fas ligand via PU box binding protein. FASEB J. https://doi.org/10.1096/fj.201902705RR

  13. 13.

    Wang HQ, Yu XD, Liu ZH et al (2011) Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J Pathol 225(2):232–242

    CAS  Article  Google Scholar 

  14. 14.

    Wu S, Gu Z, Wu Y et al (2020) LINC00324 accelerates the proliferation and migration of osteosarcoma through regulating WDR66. J Cell Physiol 235(1):339–348

    CAS  Article  Google Scholar 

  15. 15.

    Pan ZH, Guo XQ, Shan J et al (2018) LINC00324 exerts tumor-promoting functions in lung adenocarcinoma via targeting miR-615-5p/AKT1 axis. Eur Rev Med Pharmacol Sci 22(23):8333–8342

    PubMed  Google Scholar 

  16. 16.

    Sloan SR, Wipplinger C, Kirnaz S et al (2020) Combined nucleus pulposus augmentation and annulus fibrosus repair prevents acute intervertebral disc degeneration after discectomy. Sci Transl Med 12(534):eaay2380

    Article  Google Scholar 

  17. 17.

    Cheng X, Zhang G, Zhang L et al (2018) Mesenchymal stem cells deliver exogenous miR-21 via exosomes to inhibit nucleus pulposus cell apoptosis and reduce intervertebral disc degeneration. J Cell Mol Med 22(1):261–276

    CAS  Article  Google Scholar 

  18. 18.

    Xie J, Li B, Yao B et al (2020) Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment. Biosci Rep 40(2):BSR20191726. https://doi.org/10.1042/BSR20191726

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

None.

Author information

Affiliations

Authors

Contributions

YC, YW, and RC contributed to the study design; all authors collected the data and performed the data analysis; all authors prepared the manuscript.

Corresponding author

Correspondence to Rongchun Chen.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethical approval

Ethical approval was given by the Ethics Committee of the Affiliated Ganzhou Hospital of Nanchang University. All patients gave their written information consent.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chen, Y., Wu, Y., Chen, R. et al. LncRNA LINC00324 is upregulated in intervertebral disk degeneration and upregulates FasL in nucleus pulposus cells. Mol Cell Biochem (2021). https://doi.org/10.1007/s11010-021-04058-9

Download citation

Keywords

  • LINC00324
  • FasL
  • Intervertebral disk degeneration