Skip to main content

Advertisement

SpringerLink
Log in

Identification of dysregulated pathways underlying HTLV-1-associated myelopathy/tropical spastic paraparesis through co-expression network analysis

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Human T cell lymphotropic virus-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a pathogen-caused disease which is associated with the progressive neurological disorder. HAM/TSP affects the expression level of several proteins and dysregulates some biological pathways. To identify the interaction patterns among expressed genes in HAM/TSP patients, weighted gene co-expression network analysis (WGCNA) was applied. Three microarray datasets regarding HAM/TSP were merged, and the co-expression network was constructed among genes. A total of 38 modules were identified. Three preserved modules in HAM/TSP in comparison to the healthy subjects which also had the most connected proteins and enriched in the biological pathways were selected. These modules were enriched in pathways related to immune systems, cell cycle, viral infection, and neuronal systems. Moreover, the involvement of novel immunological-related proteins including C1QB, GBP5, PSME1, SERPING1, and UBE2C; neurological-related proteins including TUBA4A, TUBB8, and TP63; and also proteins including TRPC6, PRKG2, OPRD1, PRKACA, and TUBB4A involved in the cGMP-PKG signaling pathway, thyroid hormone synthesis, and recruitment of mitotic centrosome proteins and complexes were found. Therefore, tracing these proteins and the identified modules can shed light on the pathogenesis mechanism of HAM/TSP and help to find potential therapeutic targets. However, further experimental validation should be performed to confirm the proposed functional players.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

All relevant data are included in the paper. 

Code availability 

Not applicable. 

References

  • Alefantis T, Jain P, Ahuja J, Mostoller K, Wigdahl B (2005) HTLV-1 Tax nucleocytoplasmic shuttling, interaction with the secretory pathway, extracellular signaling, and implications for neurologic disease. J Biomed Sci 12(6):961–974

    Article  CAS  PubMed  Google Scholar 

  • Alfahad T, Nath A (2013) Retroviruses and amyotrophic lateral sclerosis. Antiviral Res 99(2):180–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Assone T, de Souza FV, Gaester KO, Fonseca LAM, do Carmo Luiz O, Malta F, Pinho JRR, de Toledo Gonçalves F, da Silva Duarte AJ, de Oliveira ACPJPNTD (2014) IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers. PLoS Negl Trop Dis 8(9):e3199

    Article  PubMed  PubMed Central  Google Scholar 

  • Baas PW, Ahmad FJ (2013) Beyond taxol: microtubule-based treatment of disease and injury of the nervous system. Brain 136(10):2937–2951

    Article  PubMed  PubMed Central  Google Scholar 

  • Bangham CRJAroi (2018) Human T cell leukemia virus type 1: persistence and pathogenesis. 36:43–71.

  • Bangham CRM (2018) Human T cell leukemia virus type 1: persistence and pathogenesis. Annu Rev Immunol 36:43–71

    Article  CAS  PubMed  Google Scholar 

  • Bangham CR, Araujo A, Yamano Y, Taylor GP (2015) HTLV-1-associated myelopathy/tropical spastic paraparesis. Nature reviews Disease primers 1:15012

    Article  PubMed  Google Scholar 

  • Bastian M, Heymann S, Jacomy M (2009) Gephi: an open source software for exploring and manipulating networks. In: Third international AAAI conference on weblogs and social media

  • Boxus M, Willems L (2009) Mechanisms of HTLV-1 persistence and transformation. Br J Cancer 101(9):1497–1501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boxus M, Twizere JC, Legros S, Dewulf JF, Kettmann R, Willems L (2008) The HTLV-1 Tax interactome. Retrovirology 5:76

    Article  PubMed  PubMed Central  Google Scholar 

  • Chia R, Chiò A, Traynor BJ (2018) Novel genes associated with amyotrophic lateral sclerosis: diagnostic and clinical implications. Lancet Neurol 17(1):94–102

    Article  CAS  PubMed  Google Scholar 

  • Dennis G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4(9):R60

    Article  PubMed Central  Google Scholar 

  • Dou H, Wang C, Wu X, Yao L, Zhang X, Teng S, Xu H, Liu B, Wu Q, Zhang Q, Hu M, Wang Y, Wang L, Wu Y, Shang S, Kang X, Zheng L, Zhang J, Raoux M, Lang J, Li Q, Su J, Yu X, Chen L, Zhou Z (2015) Calcium influx activates adenylyl cyclase 8 for sustained insulin secretion in rat pancreatic beta cells. Diabetologia 58(2):324–333

    Article  CAS  PubMed  Google Scholar 

  • Enose-Akahata Y, Vellucci A, Jacobson S (2017) Role of HTLV-1 Tax and HBZ in the Pathogenesis of HAM/TSP. 8 (2563).

  • Feng J, Cao Z, Wang L, Wan Y, Peng N, Wang Q, Chen X, Zhou Y, Zhu Y (2017) Inducible GBP5 mediates the antiviral response via interferon-related pathways during influenza A virus infection. Journal of innate immunity 9(4):419–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flores ER (2007) The roles of p63 in cancer. Cell Cycle 6(3):300–304

    Article  CAS  PubMed  Google Scholar 

  • Fuzii HT, da Silva Dias GA, de Barros RJ, Falcao LF, Quaresma JA (2014) Immunopathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Life Sci 104(1–2):9–14

    Article  CAS  PubMed  Google Scholar 

  • García IA, Torres Demichelis V, Viale DL, Di Giusto P, Ezhova Y, Polishchuk RS, Sampieri L, Martinez H, Sztul E, Alvarez C (2017) CREB3L1-mediated functional and structural adaptation of the secretory pathway in hormone-stimulated thyroid cells. J Cell Sci 130(24):4155–4167

    PubMed  PubMed Central  Google Scholar 

  • Ghosh M, Gharami K, Paul S, Das S (2005) Thyroid hormone-induced morphological differentiation and maturation of astrocytes involves activation of protein kinase A and ERK signalling pathway. The European journal of neuroscience 22(7):1609–1617

    Article  PubMed  Google Scholar 

  • Hasegawa H, Sano K, Ainai A, Suzuki T (2018) Application of HTLV-1 tax transgenic mice for therapeutic intervention. Advances in biological regulation 68:10–12

    Article  CAS  PubMed  Google Scholar 

  • Huo C, Wu H, Xiao J, Meng D, Zou S, Wang M, Qi P, Tian H, Hu YJFig (2019) Genomic and bioinformatic characterization of mouse mast cells (P815) upon different influenza A virus (H1N1, H5N1 and H7N2) infection. Frontiers in Genetics 10:595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang YS, Oh SW, Park SH, Lee J, Yoo JA, Kwon K, Park SJ, Kim J, Yu E, Cho JY, Lee J (2019) Melanogenic effects of maclurin are mediated through the activation of cAMP/PKA/CREB and p38 MAPK/CREB signaling pathways. Oxidative medicine and cellular longevity 2019:9827519

    Article  PubMed  PubMed Central  Google Scholar 

  • Iwasaki Y (1993) Human T cell leukemia virus type I infection and chronic myelopathy. Brain Pathol 3(1):1–10

    Article  CAS  PubMed  Google Scholar 

  • Iwasaki Y, Ohara Y, Kobayashi I, Akizuki S (1992) Infiltration of helper/inducer T lymphocytes heralds central nervous system damage in human T-cell leukemia virus infection. The American journal of pathology 140(5):1003–1008

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jain P, Ahuja J, Khan ZK, Shimizu S, Meucci O, Jennings SR, Wigdahl B (2007) Modulation of dendritic cell maturation and function by the Tax protein of human T cell leukemia virus type 1. J Leukoc Biol 82(1):44–56

    Article  CAS  PubMed  Google Scholar 

  • Ji H, Wang Y, Liu G, Chang L, Chen Z, Zhou D, Xu X, Cui W, Hong Q, Jiang L, Li J, Zhou X, Li Y, Guo Z, Zha Q, Niu Y, Weng Q, Duan S, Wang Q (2017) Elevated OPRD1 promoter methylation in Alzheimer’s disease patients. PLoS ONE 12(3):e0172335

    Article  PubMed  PubMed Central  Google Scholar 

  • Journo C, Mahieux R (2011) HTLV-1 and innate immunity. Viruses 3(8):1374–1394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang TH, Park DY, Kim W, Kim KT (2008) VRK1 phosphorylates CREB and mediates CCND1 expression. J Cell Sci 121(Pt 18):3035–3041

    Article  CAS  PubMed  Google Scholar 

  • Kannagi M, Hasegawa A, Nagano Y, Kimpara S, Suehiro Y (2019) Impact of host immunity on HTLV-1 pathogenesis: potential of Tax-targeted immunotherapy against ATL. Retrovirology 16(1):23–23

    Article  PubMed  PubMed Central  Google Scholar 

  • Kfoury Y, Nasr R, Journo C, Mahieux R, Pique C, Bazarbachi A (2012) The multifaceted oncoprotein Tax: subcellular localization, posttranslational modifications, and NF-κB activation. Adv Cancer Res 113:85–120

    Article  CAS  PubMed  Google Scholar 

  • Kimura H, Caturegli P, Takahashi M, Suzuki K (2015) New insights into the function of the immunoproteasome in immune and nonimmune cells. J Immunol Res 2015:541984–541984

    Article  PubMed  PubMed Central  Google Scholar 

  • Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9(1):559

    Article  PubMed  PubMed Central  Google Scholar 

  • Leal FE, Menezes SM, Costa EAS, Brailey PM, Gama L, Segurado AC, Kallas EG, Nixon DF, Dierckx T, Khouri R, Vercauteren J, Galvao-Castro B, Saraiva Raposo RA, Van Weyenbergh J (2018) Comprehensive antiretroviral restriction factor profiling reveals the evolutionary imprint of the ex vivo and in vivo IFN-beta response in HTLV-1-associated neuroinflammation. Frontiers in microbiology 9:985

    Article  PubMed  PubMed Central  Google Scholar 

  • Leal FE, Menezes SM, Costa EAS, Brailey PM, Gama L, Segurado AC, Kallas EG, Nixon DF, Dierckx T, Khouri R, Vercauteren J, Galvão-Castro B, Saraiva Raposo RA, Van Weyenbergh J (2018) Comprehensive antiretroviral restriction factor profiling reveals the evolutionary imprint of the ex vivo and in vivo IFN-β response in HTLV-1-associated neuroinflammation. Frontiers in microbiology 9:985

    Article  PubMed  PubMed Central  Google Scholar 

  • Li S, Pan Y, Ke R, Xie X, Zhai C, Shi W, Wang J, Yan X, Chai L, Wang Q, Zhang Q, Su X, Yang L, Gao L, Li M (2017) Inhibition of phosphodiesterase-5 suppresses calcineurin/NFAT-mediated TRPC6 expression in pulmonary artery smooth muscle cells. Scientific reports 7(1):6088

    Article  PubMed  PubMed Central  Google Scholar 

  • Lohmann SM, Vaandrager AB, Smolenski A, Walter U, De Jonge HR (1997) Distinct and specific functions of cGMP-dependent protein kinases. Trends Biochem Sci 22(8):307–312

    Article  CAS  PubMed  Google Scholar 

  • Ma R, Kang X, Zhang G, Fang F, Du Y, Lv H (2016) High expression of UBE2C is associated with the aggressive progression and poor outcome of malignant glioma. Oncology letters 11(3):2300–2304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maldonado H, Ramírez E, Utreras E, Pando ME, Kettlun AM, Chiong M, Kulkarni AB, Collados L, Puente J, Cartier L, Valenzuela MA (2011) Inhibition of cyclin-dependent kinase 5 but not of glycogen synthase kinase 3-β prevents neurite retraction and tau hyperphosphorylation caused by secretable products of human T-cell leukemia virus type I-infected lymphocytes. J Neurosci Res 89(9):1489–1498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuoka M, Jeang KT (2011) Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: viral infectivity, Tax. HBZ and therapy Oncogene 30(12):1379–1389

    Article  CAS  PubMed  Google Scholar 

  • Matsuura E, Kubota R, Tanaka Y, Takashima H, Izumo S (2015) Visualization of HTLV-1-specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. J Neuropathol Exp Neurol 74(1):2–14

    Article  CAS  PubMed  Google Scholar 

  • Mc Guire C, Beyaert R, van Loo G (2011) Death receptor signalling in central nervous system inflammation and demyelination. Trends Neurosci 34(12):619–628

    Article  CAS  PubMed  Google Scholar 

  • Medina F, Quintremil S, Alberti C, Godoy F, Pando ME, Bustamante A, Barriga A, Cartier L, Puente J, Tanaka Y, Valenzuela MA, Ramírez E (2016) Tax secretion from peripheral blood mononuclear cells and Tax detection in plasma of patients with human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis and asymptomatic carriers. J Med Virol 88(3):521–531

    Article  CAS  PubMed  Google Scholar 

  • Menezes SM, Leal FE, Dierckx T, Khouri R, Decanine D, Silva-Santos G, Schnitman SV, Kruschewsky R, Lopez G, Alvarez C, Talledo M, Gotuzzo E, Nixon DF, Vercauteren J, Brassat D, Liblau R, Vandamme AM, Galvao-Castro B, Van Weyenbergh J (2017) A Fas(hi) lymphoproliferative phenotype reveals non-apoptotic Fas signaling in HTLV-1-associated neuroinflammation. Frontiers in immunology 8:97

    Article  PubMed  PubMed Central  Google Scholar 

  • Mine H, Kawai H, Yokoi K, Akaike M, Saito S (1996) High frequencies of human T-lymphotropic virus type I (HTLV-I) infection and presence of HTLV-II proviral DNA in blood donors with anti-thyroid antibodies. J Mol Med 74(8):471–477

    Article  CAS  PubMed  Google Scholar 

  • Mohammadi A, Fazeli B, Poursina Z, Tehranian F, Vakili V, Boostani R, Rafatpanah H (2019) Htlv-1-Infected asymptomatic carriers compared to HAM/TSP patients over-express the apoptosis-and cytotoxicity-related molecules. Med Microbiol Immunol 208(6):835–844

    Article  PubMed  Google Scholar 

  • Motieghader H, Kouhsar M, Najafi A, Sadeghi B, Masoudi-Nejad A (2017) mRNA–miRNA bipartite network reconstruction to predict prognostic module biomarkers in colorectal cancer stage differentiation. Mol BioSyst 13(10):2168–2180

    Article  CAS  PubMed  Google Scholar 

  • Mozhgani SH, Jaberi N, Rezaee SA, Bustani R, Jazayeri SM, Akbarin MM, Milani S, Tarokhian H, Norouzi M (2017) Evaluation of HTLV-1 HBZ and proviral load, together with host IFN lambda3, in pathogenesis of HAM/TSP. J Med Virol 89(6):1102–1107

    Article  CAS  PubMed  Google Scholar 

  • Mozhgani SH, Jahantigh HR, Rafatpanah H, Valizadeh N, Mohammadi A, Basharkhah S, Rezaee SA (2018) Interferon lambda family along with HTLV-1 proviral load, Tax, and HBZ implicated in the pathogenesis of myelopathy/tropical spastic paraparesis. Neuro-degenerative diseases 18(2–3):150–155

    Article  CAS  PubMed  Google Scholar 

  • Mozhgani SH, Zarei-Ghobadi M, Teymoori-Rad M, Mokhtari-Azad T, Mirzaie M, Sheikhi M, Jazayeri SM, Shahbahrami R, Ghourchian H, Jafari M, Rezaee SA, Norouzi M (2018) Human T-lymphotropic virus 1 (HTLV-1) pathogenesis: a systems virology study. J Cell Biochem 119(5):3968–3979

    Article  CAS  PubMed  Google Scholar 

  • Mozhgani SH, Piran M, Zarei-Ghobadi M, Jafari M, Jazayeri SM, Mokhtari-Azad T, Teymoori-Rad M, Valizadeh N, Farajifard H, Mirzaie M, Khamseh A, Rafatpanah H, Rezaee SA, Norouzi M (2019) An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis. Retrovirology 16(1):46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nejmeddine M, Bangham CR (2010) The HTLV-1 Virological Synapse. Viruses 2(7):1427–1447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicolau-Neto P, Palumbo A, De Martino M, Esposito F, de Almeida ST, Fusco A, Nasciutti LE, Meireles Da Costa N, Ribeiro Pinto LF (2018) UBE2C is a transcriptional target of the cell cycle regulator FOXM1. Genes (Basel) 9(4):188

    Article  Google Scholar 

  • Nozuma S, Jacobson SJFim (2019) Neuroimmunology of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. Frontiers in microbiology 10:885

    Article  PubMed  PubMed Central  Google Scholar 

  • Okamoto Y, Ozaki T, Miyazaki K, Aoyama M, Miyazaki M, Nakagawara A (2003) UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme. Can Res 63(14):4167–4173

    CAS  Google Scholar 

  • Ono A, Ikeda E, Mochizuki M, Matsuoka M, Yamaguchi K, Sawada T, Yamane S, Tokudome S, Watanabe T (1998) Provirus load in patients with human T-cell leukemia virus type 1 uveitis correlates with precedent Graves’ disease and disease activities. Jpn J Cancer Res 89(6):608–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park HU, Jeong JH, Chung JH, Brady JN (2004) Human T-cell leukemia virus type 1 Tax interacts with Chk1 and attenuates DNA-damage induced G2 arrest mediated by Chk1. Oncogene 23(29):4966–4974

    Article  CAS  PubMed  Google Scholar 

  • Pumfery A, De la Fuente C, Kashanchi F (2006) HTLV-1 Tax: centrosome amplification and cancer. Retrovirology 3(1):50

    Article  PubMed  PubMed Central  Google Scholar 

  • Quaresma JA, Yoshikawa GT, Koyama RV, Dias GA, Fujihara S, Fuzii HT (2015) HTLV-1, Immune Response and Autoimmunity. Viruses 8 (1).

  • Rafatpanah H, Hedayati-Moghaddam MR, Fathimoghadam F, Bidkhori HR, Shamsian SK, Ahmadi S, Sohgandi L, Azarpazhooh MR, Rezaee SA, Farid RJJoCV (2011) High prevalence of HTLV-I infection in Mashhad, Northeast Iran: a population-based seroepidemiology survey. J Clin Virol 52(3):172–176

    Article  PubMed  Google Scholar 

  • Ramasamy A, Mondry A, Holmes CC, Altman DG (2008) Key issues in conducting a meta-analysis of gene expression microarray datasets. PLoS medicine 5(9):e184

    Article  PubMed  PubMed Central  Google Scholar 

  • Raudvere U, Kolberg L, Kuzmin I, Arak T, Adler P, Peterson H, Vilo J (2019) g: Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res 47(W1):W191–W198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roger B, Papin J, Vacher P, Raoux M, Mulot A, Dubois M, Kerr-Conte J, Voy BH, Pattou F, Charpentier G, Jonas JC, Moustaid-Moussa N, Lang J (2011) Adenylyl cyclase 8 is central to glucagon-like peptide 1 signalling and effects of chronically elevated glucose in rat and human pancreatic beta cells. Diabetologia 54(2):390–402

    Article  CAS  PubMed  Google Scholar 

  • Sanfilippo C, Cambria D, Longo A, Palumbo M, Avola R, Pinzone M, Nunnari G, Condorelli F, Musumeci G, Imbesi R, Castogiovanni P, Malaguarnera L, Di Rosa M (2017) SERPING1 mRNA overexpression in monocytes from HIV+ patients. Inflammation research : official journal of the European Histamine Research Society [et al] 66(12):1107–1116

    Article  CAS  Google Scholar 

  • Seo EJ, Efferth T, Panossian A (2018) Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells. Phytomedicine : international journal of phytotherapy and phytopharmacology 50:285–299

    Article  CAS  Google Scholar 

  • Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sontheimer RD, Racila E, Racila DM (2005) C1q: its functions within the innate and adaptive immune responses and its role in lupus autoimmunity. J Invest Dermatol 125(1):14–23

    Article  CAS  PubMed  Google Scholar 

  • Swartling FJ, Ferletta M, Kastemar M, Weiss WA, Westermark B (2009) Cyclic GMP-dependent protein kinase II inhibits cell proliferation, Sox9 expression and Akt phosphorylation in human glioma cell lines. Oncogene 28(35):3121–3131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P (2019) STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47(D1):D607–D613

    Article  CAS  PubMed  Google Scholar 

  • Takahashi S, Lin H, Geshi N, Mori Y, Kawarabayashi Y, Takami N, Mori MX, Honda A, Inoue R (2008) Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6. The Journal of physiology 586(17):4209–4223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tattermusch S, Skinner JA, Chaussabel D, Banchereau J, Berry MP, McNab FW, O’Garra A, Taylor GP, Bangham CR (2012) Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy. PLoS Pathog 8(1):e1002480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verdonck K, Gonzalez E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E (2007) Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis 7(4):266–281

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Pan F, Li S, Huang R, Wang X, Wang S, Liao X, Li D, Zhang L (2019) The prognostic value of the proteasome activator subunit gene family in skin cutaneous melanoma. J Cancer 10(10):2205–2219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong Y, Lu J, Fang Q, Lu Y, Xie C, Wu H, Yin Z (2019) UBE2C functions as a potential oncogene by enhancing cell proliferation, migration, invasion, and drug resistance in hepatocellular carcinoma cells. Bioscience reports 39 (4).

  • Yamanaka A, Hatakeyama S, Kominami K, Kitagawa M, Matsumoto M, Nakayama K (2000) Cell cycle-dependent expression of mammalian E2-C regulated by the anaphase-promoting complex/cyclosome. Mol Biol Cell 11(8):2821–2831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University Medical Sciences.  

Author information

Authors and Affiliations

  1. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mohadeseh Zarei Ghobadi

  2. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

    Mohadeseh Zarei Ghobadi

  3. Department of Microbiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran

    Sayed-Hamidreza Mozhgani

  4. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran

    Sayed-Hamidreza Mozhgani

  5. Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran

    Yousef Erfani

Authors
  1. Mohadeseh Zarei Ghobadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sayed-Hamidreza Mozhgani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yousef Erfani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MZG and YF designed the study. MZG performed bioinformatics and statistical analysis. MZG and S-HM interpreted results and wrote the manuscript. YF supervised the study. 

Corresponding author

Correspondence to Yousef Erfani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zarei Ghobadi, M., Mozhgani, SH. & Erfani, Y. Identification of dysregulated pathways underlying HTLV-1-associated myelopathy/tropical spastic paraparesis through co-expression network analysis. J. Neurovirol. 27, 820–830 (2021). https://doi.org/10.1007/s13365-020-00919-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-020-00919-z

Keywords

Search

Navigation