The circular RNA FAM169A functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR-583 and BTRC.
Adult
Animals
Base Sequence
Disease Models, Animal
Extracellular Matrix
/ metabolism
Female
Gene Expression Profiling
Gene Silencing
Humans
Intervertebral Disc Degeneration
/ diagnostic imaging
Male
MicroRNAs
/ genetics
Nucleus Pulposus
/ metabolism
Principal Component Analysis
RNA, Circular
/ genetics
Rats, Sprague-Dawley
Signal Transduction
Up-Regulation
/ genetics
beta-Transducin Repeat-Containing Proteins
/ metabolism
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
04 05 2020
04 05 2020
Historique:
received:
05
02
2020
accepted:
21
04
2020
revised:
20
04
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
23
3
2021
Statut:
epublish
Résumé
Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, although the underlying mechanisms remain poorly understood. In this study we examined the role of circular RNA FAM169A (circ-FAM169A) in degenerative nucleus pulposus (NP) tissues, and validated its function in cultured human NP cells. Overexpression of circ-FAM169A in NP cells markedly enhanced extracellular matrix (ECM) catabolism and suppressed ECM anabolism in NP cells. Furthermore, circ-FAM169A sequestered miR-583, which could potentially upregulate BTRC, an inducer of the NF-κB signaling pathway. In conclusion, the present study revealed that circ-FAM169A promotes IDD development via miR-583/BTRC signaling. These findings provide a potential therapeutic option for the treatment of IDD.
Identifiants
pubmed: 32366862
doi: 10.1038/s41419-020-2543-8
pii: 10.1038/s41419-020-2543-8
pmc: PMC7198574
doi:
Substances chimiques
MIRN583 microRNA, human
0
MicroRNAs
0
RNA, Circular
0
beta-Transducin Repeat-Containing Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
315Références
Buckwalter, J. A. Aging and degeneration of the human intervertebral disc. Spine 20, 1307–1314 (1995).
doi: 10.1097/00007632-199506000-00022
Costi, J. J., Stokes, I. A., Gardner-Morse, M. G. & Iatridis, J. C. Frequency-dependent behavior of the intervertebral disc in response to each of six degree of freedom dynamic loading: solid phase and fluid phase contributions. Spine 33, 1731–1738, (2008).
doi: 10.1097/BRS.0b013e31817bb116
Kalichman, L. & Hunter, D. J. The genetics of intervertebral disc degeneration. Familial predisposition and heritability estimation. Joint Bone Spine 75, 383–387, (2008).
doi: 10.1016/j.jbspin.2007.11.003
Samartzis, D. et al. A population-based study of juvenile disc degeneration and its association with overweight and obesity, low back pain, and diminished functional status. J. Bone Jt. Surg. Am. 93, 662–670, (2011).
doi: 10.2106/JBJS.I.01568
Friedman, B. W. et al. One-week and 3-month outcomes after an emergency department visit for undifferentiated musculoskeletal low back pain. Ann. Emerg. Med. 59, 128–133 e123, (2012).
doi: 10.1016/j.annemergmed.2011.09.012
Dudek, M. et al. The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration. Ann. Rheum. Dis. 76, 576–584, (2017).
doi: 10.1136/annrheumdis-2016-209428
Wang, J. et al. TNF-alpha and IL-1beta promote a disintegrin-like and metalloprotease with thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in intervertebral disc. J. Biol. Chem. 286, 39738–39749, (2011).
doi: 10.1074/jbc.M111.264549
Kepler, C. K. et al. Substance P stimulates production of inflammatory cytokines in human disc cells. Spine 38, E1291–1299, https://doi.org/10.1097/BRS.0b013e3182a42bc2 (2013).
doi: 10.1097/BRS.0b013e3182a42bc2
pubmed: 23873242
Risbud, M. V. & Shapiro, I. M. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat. Rev. Rheumatol. 10, 44–56, (2014).
doi: 10.1038/nrrheum.2013.160
Johnson, Z. I., Schoepflin, Z. R., Choi, H., Shapiro, I. M. & Risbud, M. V. Disc in flames: roles of TNF-alpha and IL-1beta in intervertebral disc degeneration. Eur Cell Mater. 30, 104–116 (2015).
doi: 10.22203/eCM.v030a08
Lan, P. H. et al. Landscape of RNAs in human lumbar disc degeneration. Oncotarget 7, 63166–63176, https://doi.org/10.18632/oncotarget.11334 (2016).
doi: 10.18632/oncotarget.11334
pubmed: 27542248
pmcid: 5325354
Xu, Y. Q., Zhang, Z. H., Zheng, Y. F. & Feng, S. Q. Dysregulated miR-133a mediates loss of type II collagen by directly targeting matrix metalloproteinase 9 (MMP9) in human intervertebral disc degeneration. Spine 41, E717–724, (2016).
doi: 10.1097/BRS.0000000000001375
Beermann, J., Piccoli, M. T., Viereck, J. & Thum, T. Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol. Rev. 96, 1297–1325, (2016).
doi: 10.1152/physrev.00041.2015
Ashwal-Fluss, R. et al. circRNA biogenesis competes with pre-mRNA splicing. Mol. cell 56, 55–66, (2014).
doi: 10.1016/j.molcel.2014.08.019
Vicens, Q. & Westhof, E. Biogenesis of Circular RNAs. Cell 159, 13–14, (2014).
doi: 10.1016/j.cell.2014.09.005
Zhang, X. O. et al. Complementary sequence-mediated exon circularization. Cell 159, 134–147, (2014).
doi: 10.1016/j.cell.2014.09.001
Cheng, X. et al. Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein. Ann. Rheum. Dis. 77, 770–779, (2018).
doi: 10.1136/annrheumdis-2017-212056
Guo, W. et al. Circular RNA GRB10 as a competitive endogenous RNA regulating nucleus pulposus cells death in degenerative intervertebral disk. Cell Death Dis. 9, 319, (2018).
doi: 10.1038/s41419-017-0232-z
Wang, X. et al. CircSEMA4B targets miR-431 modulating IL-1beta-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway. Biochim Biophys. Acta Mol. Basis Dis. 1864, 3754–3768, https://doi.org/10.1016/j.bbadis.2018.08.033 (2018).
doi: 10.1016/j.bbadis.2018.08.033
pubmed: 30251693
Xie, L. et al. CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis. Cell Death Dis. 10, 751, (2019).
doi: 10.1038/s41419-019-1978-2
Song, J. et al. CircularRNA_104670 plays a critical role in intervertebral disc degeneration by functioning as a ceRNA. Exp. Mol. Med 50, 94, (2018).
doi: 10.1038/s12276-018-0125-y
Barrett, T. et al. NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res 41, D991–995, https://doi.org/10.1093/nar/gks1193 (2013).
doi: 10.1093/nar/gks1193
Hansen, T. B. et al. Natural RNA circles function as efficient microRNA sponges. Nature 495, 384–388, https://doi.org/10.1038/nature11993 (2013).
doi: 10.1038/nature11993
pubmed: 23446346
Wang, H. et al. Circular RNA circ-4099 is induced by TNF-alpha and regulates ECM synthesis by blocking miR-616-5p inhibition of Sox9 in intervertebral disc degeneration. Exp. Mol. Med. 50, 27, (2018).
doi: 10.1038/s12276-018-0056-7
Zhao, C. Q., Jiang, L. S. & Dai, L. Y. Programmed cell death in intervertebral disc degeneration. Apoptosis: Int. J. Program. Cell Death 11, 2079–2088, (2006).
doi: 10.1007/s10495-006-0290-7
Kozaci, L. D., Guner, A., Oktay, G. & Guner, G. Alterations in biochemical components of extracellular matrix in intervertebral disc herniation: role of MMP-2 and TIMP-2 in type II collagen loss. Cell Biochem. Funct. 24, 431–436, https://doi.org/10.1002/cbf.1250 (2006).
doi: 10.1002/cbf.1250
pubmed: 16142692
Matsui, Y., Maeda, M., Nakagami, W. & Iwata, H. The involvement of matrix metalloproteinases and inflammation in lumbar disc herniation. Spine 23, 863–868 (1998).
doi: 10.1097/00007632-199804150-00005
Crean, J. K., Roberts, S., Jaffray, D. C., Eisenstein, S. M. & Duance, V. C. Matrix metalloproteinases in the human intervertebral disc: role in disc degeneration and scoliosis. Spine 22, 2877–2884 (1997).
doi: 10.1097/00007632-199712150-00010
Kepler, C. K., Ponnappan, R. K., Tannoury, C. A., Risbud, M. V. & Anderson, D. G. The molecular basis of intervertebral disc degeneration. Spine J. 13, 318–330, (2013).
doi: 10.1016/j.spinee.2012.12.003
Tran, C. M. et al. Transforming growth factor beta controls CCN3 expression in nucleus pulposus cells of the intervertebral disc. Arthritis Rheumatism 63, 3022–3031, https://doi.org/10.1002/art.30468 (2011).
doi: 10.1002/art.30468
pubmed: 21618206
Sivan, S. S., Wachtel, E. & Roughley, P. Structure, function, aging and turnover of aggrecan in the intervertebral disc. Biochim Biophys. Acta 1840, 3181–3189, (2014).
doi: 10.1016/j.bbagen.2014.07.013
Perera, R. S. et al. Single nucleotide variants of candidate genes in aggrecan metabolic pathway are associated with lumbar disc degeneration and modic changes. PLoS ONE 12, e0169835, (2017).
doi: 10.1371/journal.pone.0169835
Phillips, K. L. et al. Potential roles of cytokines and chemokines in human intervertebral disc degeneration: interleukin-1 is a master regulator of catabolic processes. Osteoarthr. Cartil. 23, 1165–1177, (2015).
doi: 10.1016/j.joca.2015.02.017
Zhongyi, S., Sai, Z., Chao, L. & Jiwei, T. Effects of nuclear factor kappa B signaling pathway in human intervertebral disc degeneration. Spine 40, 224–232, (2015).
doi: 10.1097/BRS.0000000000000733
Bertolo, A., Baur, M., Aebli, N., Ferguson, S. J. & Stoyanov, J. Physiological testosterone levels enhance chondrogenic extracellular matrix synthesis by male intervertebral disc cells in vitro, but not by mesenchymal stem cells. Spine J. 14, 455–468, (2014).
doi: 10.1016/j.spinee.2013.10.018
Troyanskaya, O. et al. Missing value estimation methods for DNA microarrays. Bioinforma. (Oxf., Engl.) 17, 520–525 (2001).
doi: 10.1093/bioinformatics/17.6.520
Fujita, A., Sato, J. R., Rodrigues Lde, O., Ferreira, C. E. & Sogayar, M. C. Evaluating different methods of microarray data normalization. BMC Bioinforma. 7, 469, (2006).
doi: 10.1186/1471-2105-7-469
Smyth, G. K. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. https://doi.org/10.2202/1544-6115.1027 (2004).
Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402–408, (2001).
doi: 10.1006/meth.2001.1262
Zhang, B. et al. Dysregulated MiR-3150a-3p promotes lumbar intervertebral disc degeneration by targeting aggrecan. Cell. Physiol. Biochem. 45, 2506–2515, (2018).
doi: 10.1159/000488269
Vautrot, V., Aigueperse, C., Branlant, C. & Behm-Ansmant, I. Fluorescence in situ hybridization of small non-coding RNAs. Methods Mol. Biol. 1296, 73–83, https://doi.org/10.1007/978-1-4939-2547-6_8 (2015).
doi: 10.1007/978-1-4939-2547-6_8
pubmed: 25791592
Zhang, H., La Marca, F., Hollister, S. J., Goldstein, S. A. & Lin, C. Y. Developing consistently reproducible intervertebral disc degeneration at rat caudal spine by using needle puncture. J. Neurosurg. Spine 10, 522–530, (2009).
doi: 10.3171/2009.2.SPINE08925
Masuda, K. et al. A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine 30, 5–14 (2005).
doi: 10.1097/01.brs.0000148152.04401.20
Pfirrmann, C. W., Metzdorf, A., Zanetti, M., Hodler, J. & Boos, N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 26, 1873–1878 (2001).
doi: 10.1097/00007632-200109010-00011