Open Access

MAP‑1B, PACS‑2 and AHCYL1 are regulated by miR‑34A/B/C and miR‑449 in neuroplasticity following traumatic spinal cord injury in rats: Preliminary explorative results from microarray data

  • Authors:
    • Hongshi Cao
    • Yu Zhang
    • Zhe Chu
    • Bolun Zhao
    • Haiyan Wang
    • Libin An
  • View Affiliations

  • Published online on: July 30, 2019     https://doi.org/10.3892/mmr.2019.10538
  • Pages: 3011-3018
  • Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Spinal cord injury (SCI) is a specific type of damage to the central nervous system causing temporary or permanent changes in its function. The present aimed to identify the genetic changes in neuroplasticity following SCI in rats. The GSE52763 microarray dataset, which included 15 samples [3 sham (1 week), 4 injury only (1 week), 4 injury only (3 weeks), 4 injury + treadmill (3 weeks)] was downloaded from the Gene Expression Omnibus database. An empirical Bayes linear regression model in limma package was used to identify the differentially expressed genes (DEGs) in injury vs. sham and treadmill vs. non‑treadmill comparison groups. Subsequently, time series and enrichment analyses were performed using pheatmap and clusterProfile packages, respectively. Additionally, protein‑protein interaction (PPI) and transcription factor (TF)‑microRNA (miRNA)‑target regulatory networks were constructed using Cytoscape software. In total, 159 and 105 DEGs were identified in injury vs. sham groups and treadmill vs. non‑treadmill groups, respectively. There were 40 genes in cluster 1 that presented increased expression levels in the injury (1 week/3 weeks) groups compared with the sham group, and decreased expression levels in the injury + treadmill group compared with the injury only groups; conversely, 52 genes in cluster 2 exhibited decreased expression levels in the injury (1 week/3 weeks) groups compared with the sham group, and increased expression levels in the injury + treadmill group compared with the injury only groups. Enrichment analysis indicated that clusters 1 and 2 were associated with immune response and signal transduction, respectively. Furthermore, microtubule associated protein 1B, phosphofurin acidic cluster sorting protein 2 and adenosylhomocysteinase‑like 1 exhibited the highest degrees in the regulatory network, and were regulated by miRNAs including miR‑34A, miR‑34B, miR‑34C and miR‑449. These miRNAs and their target genes may serve important roles in neuroplasticity following traumatic SCI in rats. Nevertheless, additional in‑depth studies are required to confirm these data.

References

1 

Chen Y, He Y and DeVivo MJ: Changing demographics and injury profile of new traumatic spinal cord injuries in the United States, 1972–2014. Arch Phys Med Rehabil. 97:1610–1619. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Lenehan B, Street J, Kwon BK, Noonan V, Zhang H, Fisher CG and Dvorak MF: The epidemiology of traumatic spinal cord injury in British Columbia, Canada. Spine (Phila Pa 1976). 37:321–329. 2012. View Article : Google Scholar : PubMed/NCBI

3 

DeVivo MJ and Chen Y: Trends in new injuries, prevalent cases, and aging with spinal cord injury. Arch Phys Med Rehabil. 92:332–338. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Hurlbert RJ, Hadley MN, Walters BC, Aarabi B, Dhall SS, Gelb DE, Rozzelle CJ, Ryken TC and Theodore N: Pharmacological therapy for acute spinal cord injury. Neurosurgery. 76 (Suppl 1):S71–S83. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Scarisbrick IA, Sabharwal P, Cruz H, Larsen N, Vandell AG, Blaber SI, Ameenuddin S, Papke LM, Fehlings MG, Reeves RK, et al: Dynamic role of kallikrein 6 in traumatic spinal cord injury. Eur J Neurosci. 24:1457–1469. 2010. View Article : Google Scholar

6 

Lemarchant S, Pruvost M, Hébert M, Gauberti M, Hommet Y, Briens A, Maubert E, Gueye Y, Féron F, Petite D, et al: tPA promotes ADAMTS-4-induced CSPG degradation, thereby enhancing neuroplasticity following spinal cord injury. Neurobiol Dis. 66:28–42. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Koehn LM, Noor NM, Dong Q, Er SY, Rash LD, King GF, Dziegielewska KM, Saunders NR and Habgood MD: Selective inhibition of ASIC1a confers functional and morphological neuroprotection following traumatic spinal cord injury. Version 2. F1000Res. 5:18222016. View Article : Google Scholar : PubMed/NCBI

8 

Liu NK, Wang XF, Lu QB and Xu XM: Altered microRNA expression following traumatic spinal cord injury. Exp Neurol. 219:424–429. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Ning B, Gao L, Liu RH, Liu Y, Zhang NS and Chen ZY: microRNAs in spinal cord injury: Potential roles and therapeutic implications. Int J Biol Sci. 10:997–1006. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Shin HY, Kim H, Kwon MJ, Hwang DH, Lee K and Kim BG: Molecular and cellular changes in the lumbar spinal cord following thoracic injury: Regulation by treadmill locomotor training. PLoS One. 9:e882152014. View Article : Google Scholar : PubMed/NCBI

11 

Yang Z, Lv Q, Wang Z, Dong X, Yang R and Zhao W: Identification of crucial genes associated with rat traumatic spinal cord injury. Mol Med Rep. 15:1997–2006. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Liu Q, Zhang B, Liu C and Zhao D: Molecular mechanisms underlying the positive role of treadmill training in locomotor recovery after spinal cord injury. Spinal Cord. 55:441–446. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, et al: NCBI GEO: Archive for functional genomics data sets-update. Nucleic Acids Res. 41:D991–D995. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Carvalho BS and Irizarry RA: A framework for oligonucleotide microarray preprocessing. Bioinformatics. 26:2363–2367. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W and Smyth GK: Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43:e472015. View Article : Google Scholar : PubMed/NCBI

16 

Kolde R: pheatmap: Pretty Heatmaps. R package version 0.6.1. 2013. simplehttp://CRAN.R-project.org/packageepheatmapOct 12–2015

17 

Yu G, Wang LG, Han Y and He QY: clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS. 16:284–287. 2012. View Article : Google Scholar : PubMed/NCBI

18 

The Gene Ontology Consortium, . Expansion of the gene ontology knowledgebase and resources. Nucleic Acids Research. 45:D331–D338. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Mi H, Huang X, Muruganujan A, Tang H, Mills C, Kang D and Thomas PD: PANTHER version 11: Expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements. Nucleic Acids Res. 45:D183–D189. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Kanehisa M and Goto S: KEGG: Kyoto encyclopaedia of genes and genomes. Nucleic Acids Res. 28:27–30. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, et al: STRING v10: Protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 43:D447–D452. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Tang Y, Li M, Wang J, Pan Y and Wu FX: CytoNCA: A cytoscape plugin for centrality analysis and evaluation of protein interaction networks. Biosystems. 127:67–72. 2015. View Article : Google Scholar : PubMed/NCBI

24 

He X and Zhang J: Why do hubs tend to be essential in protein networks? PLoS Genet. 2:e882006. View Article : Google Scholar : PubMed/NCBI

25 

Wang J, Duncan D, Shi Z and Zhang B: WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): Update 2013. Nucleic Acids Res. 41:W77–W83. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Gonzalez-Billault C, Jimenez-Mateos EM, Caceres A, Diaz-Nido J, Wandosell F and Avila J: Microtubule-associated protein 1B function during normal development, regeneration, and pathological conditions in the nervous system. J Neurobiol. 58:48–59. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Ma D, Nothias F, Boyne LJ and Fischer I: Differential regulation of microtubule-associated protein 1B (MAP1B) in rat CNS and PNS during development. J Neurosci Res. 49:319–332. 1997. View Article : Google Scholar : PubMed/NCBI

28 

Gödel M, Temerinac D, Grahammer F, Hartleben B, Kretz O, Riederer BM, Propst F, Kohl S and Huber TB: Microtubule associated protein 1b (MAP1B) is a marker of the microtubular cytoskeleton in podocytes but is not essential for the function of the kidney filtration barrier in mice. PLoS One. 10:e01401162015. View Article : Google Scholar : PubMed/NCBI

29 

Tortosa E, Montenegro-Venegas C, Benoist M, Härtel S, González-Billault C, Esteban JA and Avila J: Microtubule-associated protein 1B (MAP1B) is required for dendritic spine development and synaptic maturation. J Biol Chem. 286:40638–40648. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Köttgen M, Benzing T, Simmen T, Tauber R, Buchholz B, Feliciangeli S, Huber TB, Schermer B, Kramer-Zucker A, Höpker K, et al: Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion channel regulation. EMBO J. 24:705–716. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Liu WM, Wu JY, Li FC and Chen QX: Ion channel blockers and spinal cord injury. J Neurosci Res. 89:791–801. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Kawaai K, Mizutani A, Shoji H, Ogawa N, Ebisui E, Kuroda Y, Wakana S, Miyakawa T, Hisatsune C and Mikoshiba K: IRBIT regulates CaMKIIα activity and contributes to catecholamine homeostasis through tyrosine hydroxylase phosphorylation. Proc Natl Acad Sci USA. 112:5515–5520. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Jauhari A, Singh T, Singh P, Parmar D and Yadav S: Regulation of miR-34 family in neuronal development. Mol Neurobiol. 55:936–945. 2018. View Article : Google Scholar : PubMed/NCBI

34 

Aranha MM, Santos DM, Solá S, Steer CJ and Rodrigues CM: miR-34a regulates mouse neural stem cell differentiation. PLoS One. 6:e213962011. View Article : Google Scholar : PubMed/NCBI

35 

Rokavec M, Li H, Jiang L and Hermeking H: The p53/miR-34 axis in development and disease. J Mol Cell Biol. 6:214–230. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Zhu Y, Wu Y and Zhang R: Electro-acupuncture promotes the proliferation of neural stem cells and the survival of neurons by downregulating miR-449a in rat with spinal cord injury. EXCLI J. 16:363–374. 2017.PubMed/NCBI

37 

Han R, Ji X, Rong R, Li Y, Yao W, Yuan J, Wu Q, Yang J, Yan W, Han L, et al: MiR-449a regulates autophagy to inhibit silica-induced pulmonary fibrosis through targeting Bcl2. J Mol Med (Berl). 94:1267–1279. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Kanno H, Ozawa H, Sekiguchi A and Itoi E: The role of autophagy in spinal cord injury. Autophagy. 5:390–392. 2009. View Article : Google Scholar : PubMed/NCBI

39 

Li H, Zhang Q, Yang X and Wang L: PPAR-γ agonist rosiglitazone reduces autophagy and promotes functional recovery in experimental traumaticspinal cord injury. Neurosci Lett. 650:89–96. 2017. View Article : Google Scholar : PubMed/NCBI

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October 2019
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Copy and paste a formatted citation
APA
Cao, H., Zhang, Y., Chu, Z., Zhao, B., Wang, H., & An, L. (2019). MAP‑1B, PACS‑2 and AHCYL1 are regulated by miR‑34A/B/C and miR‑449 in neuroplasticity following traumatic spinal cord injury in rats: Preliminary explorative results from microarray data. Molecular Medicine Reports, 20, 3011-3018. https://doi.org/10.3892/mmr.2019.10538
MLA
Cao, H., Zhang, Y., Chu, Z., Zhao, B., Wang, H., An, L."MAP‑1B, PACS‑2 and AHCYL1 are regulated by miR‑34A/B/C and miR‑449 in neuroplasticity following traumatic spinal cord injury in rats: Preliminary explorative results from microarray data". Molecular Medicine Reports 20.4 (2019): 3011-3018.
Chicago
Cao, H., Zhang, Y., Chu, Z., Zhao, B., Wang, H., An, L."MAP‑1B, PACS‑2 and AHCYL1 are regulated by miR‑34A/B/C and miR‑449 in neuroplasticity following traumatic spinal cord injury in rats: Preliminary explorative results from microarray data". Molecular Medicine Reports 20, no. 4 (2019): 3011-3018. https://doi.org/10.3892/mmr.2019.10538