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Regulation of Apoptosis and Inflammatory Response in Interleukin-1β-Induced Nucleus Pulposus Cells by miR-125b-5p Via Targeting TRIAP1

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Abstract

The aim of the present study was to determine the function of microRNA (miR)-125b-5p in lumbar disc degeneration (LDD). Nucleus pulposus (NP) cells were stimulated with 10 ng/ml IL-1β for 24 h to establish an LDD model. Reverse transcription-quantitative PCR was used to assess miR-125b-5p levels in human lumbar degenerative NP samples and IL-1β-treated NP cells. An interaction between miR-125b-5p and TP53-regulated inhibitor of apoptosis 1 (TRIAP1) was revealed by TargetScan 7.1 and dual-luciferase reporter assay. Protein levels of pro-inflammatory factors were determined using ELISA. Cell viability and apoptosis were evaluated by MTT and flow cytometry analysis, respectively. miR-125b-5p was markedly upregulated in both human lumbar degenerative NP specimens and IL-1β-treated NP cells. TRIAP1, which directly targets miR-125b-5p, was markedly downregulated in human lumbar degenerative NP specimens and IL-1β-treated NP cells. The levels of TNF-α and IL-6 were inhibited in IL-1β-treated NP cells transfected with miR-125b-5p inhibitor. Moreover, miR-125b-5p inhibitor increased NP cell viability, prevented apoptosis and repressed the apoptotic peptidase activating factor 1/caspase 9 pathway in IL-1β-treated NP cells. Thus, the present findings suggested that miR-125b-5p could regulate LDD by adjusting NP cell apoptosis and inflammatory responses via TRIAP1.

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References

  • Abdollahzade S, Hanaei S, Sadr M et al (2018) Significant association of TNF-α, but not other pro-inflammatory cytokines, single nucleotide polymorphisms with intervertebral disc degeneration in Iranian population. Clin Neurol Neurosurg 173:77–83

    Article  PubMed  Google Scholar 

  • Adams MA, Roughley PJ (2006) What is intervertebral disc degeneration, and what causes it? Spine 31:2151–2161

    Article  PubMed  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  • Cai P, Yang T, Jiang X et al (2017) Role of miR-15a in intervertebral disc degeneration through targeting MAP3K9. Biomed Pharmacother 87:568–574

    Article  CAS  PubMed  Google Scholar 

  • Cao W, Qian G, Luo W et al (2018) miR-125b is downregulated in systemic lupus erythematosus patients and inhibits autophagy by targeting UVRAG. Biomed Pharmacother 99:791–797

    Article  CAS  PubMed  Google Scholar 

  • Colombier P, Clouet J, Hamel O et al (2014) The lumbar intervertebral disc: from embryonic development to degeneration. Jt Bone Spine 81:125–129

    Article  Google Scholar 

  • Diao W, Lu L, Li S et al (2017) MicroRNA-125b-5p modulates the inflammatory state of macrophages via targeting B7-H4. Biochem Biophys Res Commun 491:912–918

    Article  CAS  PubMed  Google Scholar 

  • Du L, Pertsemlidis A (2011) Cancer and neurodegenerative disorders: pathogenic convergence through microRNA regulation. J Mol Cell Biol 3:176–180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ell B, Kang Y (2014) MicroRNAs as regulators of bone homeostasis and bone metastasis. Bonekey Rep 3:549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farrokhi MR, Karimi MH, Ghaffarpasand F et al (2020) MicroRNA-199a upregulation mediates lumbar intervertebral disc degeneration and is associated with clinical grades of degeneration. Turk Neurosurg 30:104–111

    PubMed  Google Scholar 

  • Fook-Alves VL, de Oliveira MB, Zanatta DB et al (2016) TP53 Regulated Inhibitor of Apoptosis 1 (TRIAP1) stable silencing increases late apoptosis by upregulation of caspase 9 and APAF1 in RPMI8226 multiple myeloma cell line. Biochim Biophys Acta 1862:1105–1110

    Article  CAS  PubMed  Google Scholar 

  • Freemont AJ (2009) The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology 48:5–10

    Article  CAS  PubMed  Google Scholar 

  • Ge FX, Li H, Yin X (2017) Upregulation of microRNA-125b-5p is involved in the pathogenesis of osteoarthritis by downregulating SYVN1. Oncol Rep 37:2490–2496

    Article  CAS  PubMed  Google Scholar 

  • Hammond SM (2015) An overview of microRNAs. Adv Drug Deliv Rev 87:3–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu B, Xu C, Tian Y, Shi C et al (2017) Inflammatory microRNA-194 and -515 attenuate the biosynthesis of chondroitin sulfate during human intervertebral disc degeneration. Oncotarget 8:49303–49317

    Article  PubMed  PubMed Central  Google Scholar 

  • Kanna RM, Shetty AP, Rajasekaran S (2014) Patterns of lumbar disc degeneration are different in degenerative disc disease and disc prolapse magnetic resonance imaging analysis of 224 patients. Spine J 14:300–307

    Article  PubMed  Google Scholar 

  • Li Z, Shen J, Wu WK et al (2013) The role of leptin on the organization and expression of cytoskeleton elements in nucleus pulposus cells. J Orthop Res 31:847–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Liang J, Wu WK et al (2014) Leptin activates RhoA/ROCK pathway to induce cytoskeleton remodeling in nucleus pulposus cells. Int J Mol Sci 15:1176–1188

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li G, Tang X, Chen H et al (2018a) miR-148a inhibits pro-inflammatory cytokines released by intervertebral disc cells by regulating the p38/MAPK pathway. Exp Ther Med 16:2665–2669

    PubMed  PubMed Central  Google Scholar 

  • Li Y, Wang Y, Fan H et al (2018b) miR-125b-5p inhibits breast cancer cell proliferation, migration and invasion by targeting KIAA1522. Biochem Biophys Res Commun 504:277–282

    Article  CAS  PubMed  Google Scholar 

  • Liu G, Cao P, Chen H et al (2013) MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K. PLoS One 8:e75251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu H, Huang X, Liu X et al (2014) miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling. Int J Mol Sci 15:4007–4018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu P, Chang F, Zhang T et al (2017) Downregulation of microRNA-125a is involved in intervertebral disc degeneration by targeting pro-apoptotic Bcl-2 antagonist killer 1. Iran J Basic Med Sci 20:1260–1267

    PubMed  PubMed Central  Google Scholar 

  • Lv F, Huang Y, Lv W et al (2017) MicroRNA-146a ameliorates inflammation via TRAF6/NF-κB pathway in intervertebral disc cells. Med Sci Monit 23:659–664

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lv J, Li S, Wan T et al (2018) Inhibition of microRNA-30d attenuates the apoptosis and extracellular matrix degradation of degenerative human nucleus pulposus cells by up-regulating SOX9. Chem Biol Interact 296:89–97

    Article  CAS  PubMed  Google Scholar 

  • Mayer JE, Iatridis JC, Chan D et al (2013) Genetic polymorphisms associated with intervertebral disc degeneration. Spine J 13:299–317

    Article  PubMed  PubMed Central  Google Scholar 

  • Molinos M, Almeida CR, Caldeira J et al (2015) Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface 12:20150429

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohrt-Nissen S, Døssing KB, Rossing M et al (2013) Characterization of miRNA expression in human degenerative lumbar disks. Connect Tissue Res 54:197–203

    Article  CAS  PubMed  Google Scholar 

  • Park WR, Nakamura Y (2005) p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway. Cancer Res 65:1197–1206

    Article  CAS  PubMed  Google Scholar 

  • Potting C, Tatsuta T, König T et al (2013) TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid. Cell Metab 18:287–295

    Article  CAS  PubMed  Google Scholar 

  • Shen Y, Shen Z, Guo L et al (2018) MiR-125b-5p is involved in oxygen and glucose deprivation injury in PC-12 cells via CBS/H2S pathway. Nitric Oxide 78:11–21

    Article  CAS  PubMed  Google Scholar 

  • Singh RP, Massachi I, Manickavel S et al (2013) The role of miRNA in inflammation and autoimmunity. Autoimmun Rev 12:1160–1165

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Hong J, Sun S et al (2018) Transcription factor 7-like 2 controls matrix degradation through nuclear factor κB signaling and is repressed by microRNA-155 in nucleus pulposus cells. Biomed Pharmacother 108:646–655

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Wang B, Zou M et al (2018a) CircSEMA4B targets miR-431 modulating IL-1β-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway. Biochim Biophys Acta Mol Basis Dis 1864:3754–3768

    Article  CAS  Google Scholar 

  • Wang X, Meng Q, Qiu C et al (2018b) Potential therapeutic role of Co-Q10 in alleviating intervertebral disc degeneration and suppressing IL-1β-mediated inflammatory reaction in NP cells. Int Immunopharmacol 64:424–431

    Article  CAS  PubMed  Google Scholar 

  • Xiu L, Xing Q, Mao J et al (2018) miRNA-125b-5p suppresses hypothyroidism development by targeting signal transducer and activator of transcription 3. Med Sci Monit 24:5041–5049

    Article  PubMed  Google Scholar 

  • Xu YQ, Zhang ZH, Zheng YF et al (2016) Dysregulated miR-133a mediates loss of type II collagen by directly targeting matrix metalloproteinase 9 (MMP9) in human intervertebral disc degeneration. Spine (Phila Pa 1976) 41:717–724

    Article  Google Scholar 

  • Yang H, Cao C, Wu C et al (2015) TGF-βl suppresses inflammation in cell therapy for intervertebral disc degeneration. Sci Rep 5:13254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu X, Li Z, Shen J et al (2013) MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PLoS One 8:e83080

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang YL, Chen XQ (2020) Dysregulation of microRNA-770-5p influences pancreatic-β-cell function by targeting TP53 regulated inhibitor of apoptosis 1 in gestational diabetes mellitus. Eur Rev Med Pharmacol Sci 24:793–801

    PubMed  Google Scholar 

  • Zhang B, Guo W, Sun C et al (2018) Dysregulated MiR-3150a-3p promotes lumbar intervertebral disc degeneration by targeting aggrecan. Cell Physiol Biochem 45:2506–2515

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Cong R, Zhao K et al (2019a) High TRIAP1 expression in penile carcinoma is associated with high risk of recurrence and poor survival. Ann Transl Med 7:330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang SZ, Qiu XJ, Dong SS et al (2019b) MicroRNA-770-5p is involved in the development of diabetic nephropathy through regulating podocyte apoptosis by targeting TP53 regulated inhibitor of apoptosis 1. Eur Rev Med Pharmacol Sci 23:1248–1256

    PubMed  Google Scholar 

  • Zhou XG, Huang XL, Liang SY et al (2018) Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis. Onco Targets Ther 11:2815–2830

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhu C, Jiang W, Cheng Q et al (2018) Hemeoxygenase-1 suppresses IL-1β-induced apoptosis through the NF-κB pathway in human degenerative nucleus pulposus cells. Cell Physiol Biochem 46:644–653

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedics, Pukou Branch Hospital of Jiangsu Province Hospital, Nanjing Pukou Central Hospital, 166 Shanghe Street, Pukou, Nanjing, 211800, Jiangsu, People’s Republic of China

    Jian Jie, Xiaoming Xu, Weilin Li & Guihua Wang

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  1. Jian Jie
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  2. Xiaoming Xu
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  3. Weilin Li
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  4. Guihua Wang
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Correspondence to Jian Jie.

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Jie, J., Xu, X., Li, W. et al. Regulation of Apoptosis and Inflammatory Response in Interleukin-1β-Induced Nucleus Pulposus Cells by miR-125b-5p Via Targeting TRIAP1. Biochem Genet 59, 475–490 (2021). https://doi.org/10.1007/s10528-020-10009-8

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