Identification of hub genes and molecular pathways in human T-lymphotropic virus type 1 associated diseases using protein-protein interactions networks
Abstract
Background and Objectives: Human T-lymphotropic virus type 1 (HTLV-1) is the cause of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The present study aims to analyze gene expression patterns in ATL and HAM/TSP.
Materials and Methods: Microarray gene expression profiling of T-lymphocytes from HTLV-1 associated disease and healthy control were obtained from Gene Expression Omnibus (GEO). Several bioinformatics tools were used to identify differentially expressed genes (DEGs). Among the generated DEGs, we constructed protein-protein interaction (PPI) between HAM/TSM and ATL in comparison to asymptomatic carriers (ACs). Subsequently, gene ontology (GO) and topological analysis were performed.
Results: We found that the majority of DEGs in ATL and HAM/TSP were importantly implicated in immune response categories. The nodes and edges number of normal-AC, AC-ATL and ATL-HAM/TSP PPIs were 168 and 145, 116 and 97, and 275 and 327, respectively. Based on the topological analyses of protein-protein interaction networks, APP (Amyloid Beta Precursor Protein) was detected as a critical player in progression of HTLV-1 disease.
Conclusion: Dysregulation of immune response associated transcripts play a critical role in HTLV-1 disease progression. Immune response associated genes may be biomarker for prognosis in cancer development and therapeutic targets.
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26. Nguyen KV. β-Amyloid precursor protein (APP) and the human diseases. AIMS Neurosci 2019;6:273-281.
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28. Sokol DK, Maloney B, Long JM, Ray B, Lahiri DK. Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology 2011;76:1344-1352.
29. Sondag CM, Combs CK. Amyloid precursor protein mediates proinflammatory activation of monocytic lineage cells. J Biol Chem 2004;279:14456-14463.
30. Puig KL, Swigost AJ, Zhou X, Sens MA, Combs CK. Amyloid precursor protein expression modulates intestine immune phenotype. J Neuroimmune Pharmacol 2012;7:215-230.
31. Carrano A, Das P. Altered innate immune and glial cell responses to inflammatory stimuli in amyloid precursor protein knockout mice. PLoS One 2015;10(10):e0140210.
32. Yamano Y, Coler-Reilly A. HTLV-1 induces a Th1-like state in CD4+ CCR4+ T cells that produces an inflammatory positive feedback loop via astrocytes in HAM/TSP. J Neuroimmunol 2017;304:51-55.
33. Liu Y, Shi SL. The roles of hnRNP A2/B1 in RNA biology and disease. Wiley Interdiscip Rev RNA 2021;12(2):e1612.
34. Wang S, Xu G, Chao F, Zhang C, Han D, Chen G. HNRNPC promotes proliferation, metastasis and predicts prognosis in prostate cancer. Cancer Manag Res 2021;13:7263-7276.
35. Zhang Q, Zhang J, Ye J, Li X, Liu H, Ma X, et al. Nuclear speckle specific hnRNP D-like prevents age-and AD-related cognitive decline by modulating RNA splicing. Mol Neurodegener 2021;16:66.
36. Jeong SJ, Pise-Masison CA, Radonovich MF, Park HU, Brady JN. Activated AKT regulates NF-kappaB activation, p53 inhibition and cell survival in HTLV-1-transformed cells. Oncogene 2005;24:6719-6728.
2. Schierhout G, McGregor S, Gessain A, Einsiedel L, Martinello M, Kaldor J. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet Infect Dis 2020;20:133-143.
3. Morales-Sanchez A, Fuentes-Panana EM. Human viruses and cancer. Viruses 2014;6:4047-4079.
4. Rosadas C, Taylor GP. Mother-to-child HTLV-1 transmission: unmet research needs. Front Microbiol 2019;10:999.
5. Poetker SK, Porto AF, Giozza SP, Muniz AL, Caskey MF, Carvalho EM, et al. Clinical manifestations in individuals with recent diagnosis of HTLV type I infection. J Clin Virol 2011;51:54-58.
6. Araujo AQC, Wedemann D. HTLV-1 associated neurological complex. What is hidden below the water? AIDS Rev 2019;21:211-217.
7. Nozuma S, Jacobson S. Neuroimmunology of human t-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. Front Microbiol 2019;10:885.
8. Iqbal J, Wright G, Wang C, Rosenwald A, Gascoyne RD, Weisenburger DD, et al. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood 2014;123:2915-2923.
9. Yasunaga J, Matsuoka M. Molecular mechanisms of HTLV-1 infection and pathogenesis. Int J Hematol 2011;94:435-442.
10. Naito T, Yasunaga JI, Mitobe Y, Shirai K, Sejima H, Ushirogawa H, et al. Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP. Retrovirology 2018;15:72.
11. Cieslik M, Chinnaiyan AM. Cancer transcriptome profiling at the juncture of clinical translation. Nat Rev Genet 2018;19:93-109.
12. Mitra S, Das S, Chakrabarti J. Systems biology of cancer biomarker detection. Cancer Biomark 2013;13:201-213.
13. Yang X, Kui L, Tang M, Li D, Wei K, Chen W, et al. High-throughput transcriptome profiling in drug and biomarker discovery. Front Genet 2020;11:19.
14. Hall PA, Reis-Filho JS, Tomlinson IP, Poulsom R. An introduction to genes, genomes and disease. J Pathol 2010;220:109-113.
15. Heidecker B, Hare JM. The use of transcriptomic biomarkers for personalized medicine. Heart Fail Rev 2007;12:1-11.
16. Clough E, Barrett T. The Gene Expression Omnibus Database. Methods Mol Biol 2016;1418:93-110.
17. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res 2013;41:D991-D995.
18. Maere S, Heymans K, Kuiper M. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 2005;21:3448-3449.
19. Wang K, Lee I, Carlson G, Hood L, Galas D. Systems biology and the discovery of diagnostic biomarkers. Dis Markers 2010;28:199-207.
20. Parikh JR, Klinger B, Xia Y, Marto JA, Blüthgen N. Discovering causal signaling pathways through gene-expression patterns. Nucleic acids Res 2010;38:W109-W117.
21. Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000;28:27-30.
22. Martin A, Ochagavia ME, Rabasa LC, Miranda J, Fernandez-de-Cossio J, Bringas R. BisoGenet: a new tool for gene network building, visualization and analysis. BMC Bioinformatics 2010;11:91.
23. Hillmer RA. Systems biology for biologists. PLoS Pathog 2015;11(5):e1004786.
24. Baumkötter F, Schmidt N, Vargas C, Schilling S, Weber R, Wagner K, et al. Amyloid precursor protein dimerization and synaptogenic function depend on copper binding to the growth factor-like domain. J Neurosci 2014;34:11159-11172.
25. Tang K, Wang C, Shen C, Sheng S, Ravid R, Jing N. Identification of a novel alternative splicing isoform of human amyloid precursor protein gene, APP639. Eur J Neurosci 2003;18:102-108.
26. Nguyen KV. β-Amyloid precursor protein (APP) and the human diseases. AIMS Neurosci 2019;6:273-281.
27. Paudel YN, Angelopoulou E, Piperi C, Othman I, Aamir K, Shaikh MF. Impact of HMGB1, RAGE, and TLR4 in Alzheimer’s disease (AD): from risk factors to therapeutic targeting. Cells 2020;9:383.
28. Sokol DK, Maloney B, Long JM, Ray B, Lahiri DK. Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology 2011;76:1344-1352.
29. Sondag CM, Combs CK. Amyloid precursor protein mediates proinflammatory activation of monocytic lineage cells. J Biol Chem 2004;279:14456-14463.
30. Puig KL, Swigost AJ, Zhou X, Sens MA, Combs CK. Amyloid precursor protein expression modulates intestine immune phenotype. J Neuroimmune Pharmacol 2012;7:215-230.
31. Carrano A, Das P. Altered innate immune and glial cell responses to inflammatory stimuli in amyloid precursor protein knockout mice. PLoS One 2015;10(10):e0140210.
32. Yamano Y, Coler-Reilly A. HTLV-1 induces a Th1-like state in CD4+ CCR4+ T cells that produces an inflammatory positive feedback loop via astrocytes in HAM/TSP. J Neuroimmunol 2017;304:51-55.
33. Liu Y, Shi SL. The roles of hnRNP A2/B1 in RNA biology and disease. Wiley Interdiscip Rev RNA 2021;12(2):e1612.
34. Wang S, Xu G, Chao F, Zhang C, Han D, Chen G. HNRNPC promotes proliferation, metastasis and predicts prognosis in prostate cancer. Cancer Manag Res 2021;13:7263-7276.
35. Zhang Q, Zhang J, Ye J, Li X, Liu H, Ma X, et al. Nuclear speckle specific hnRNP D-like prevents age-and AD-related cognitive decline by modulating RNA splicing. Mol Neurodegener 2021;16:66.
36. Jeong SJ, Pise-Masison CA, Radonovich MF, Park HU, Brady JN. Activated AKT regulates NF-kappaB activation, p53 inhibition and cell survival in HTLV-1-transformed cells. Oncogene 2005;24:6719-6728.
| Files | ||
| Issue | Vol 14 No 1 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v14i1.8814 | |
| Keywords | ||
| Human T-lymphotropic virus 1; Adult T-cell leukemia; Human T lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis; Gene expression; DEGs; Gene ontology | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Ebadi A, Momenifar N, Yazdani S, Gholizadeh O, Poortahmasebi V. Identification of hub genes and molecular pathways in human T-lymphotropic virus type 1 associated diseases using protein-protein interactions networks. Iran J Microbiol. 2022;14(1):125-132.
