Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
NeuroMolecular Medicine
Published in: NeuroMolecular Medicine 1/2020

01-03-2020 | Multiple Sclerosis | Original Paper

The Putative Association of TOB1-AS1 Long Non-coding RNA with Immune Tolerance: A Study on Multiple Sclerosis Patients

Authors: Reyhaneh Dehghanzad, Majid Pahlevan Kakhki, Asieh Alikhah, Mohammad Ali Sahraian, Mehrdad Behmanesh

Published in: NeuroMolecular Medicine | Issue 1/2020

Login to get access

Abstract

The hallmark of multiple sclerosis (MS) pathogenesis is the breakdown of peripheral tolerance in the immune system. However, its molecular mechanism is not completely understood. Since long non-coding RNAs (lncRNAs) has played important roles in regulation of immunological pathways, here, we evaluated the expression of a novel lncRNA, TOB1-AS1, and its putative associated coding genes in the mechanism of maintaining immune tolerance in peripheral blood of MS patients to assess their possible roles in MS pathogenesis. In this study, 39 MS patients and 32 healthy matched controls were recruited. Real-time PCR standard curve method was used to quantify transcript levels of TOB1-AS1, TOB1, SKP2, and TSG. In addition, the potential sex hormone receptor binding sites on target genes promoter were analyzed using JASPR software. This work demonstrates a negative correlation between TOB1-AS1 expression and EDSS of patients. Also, a robust dysregulation of co-expression of TOB1-AS1 lncRNA and the coding genes in MS patients compared to controls was observed. Such dysregulation in this pathway may be related to MS pathogenesis and response to interferon treatment.
Literature
Arloth, J. (2014). Expression quantitative trait loci as possible biomarkers on depression: Candidate gene and genome-wide approaches.
Atianand, M. K., & Fitzgerald, K. A. (2014). Long non-coding RNAs and control of gene expression in the immune system. Trends in Molecular Medicine,20(11), 623–631.PubMedPubMedCentral
Baranzini, S. E. (2014). Role of antiproliferative gene Tob1 in the immune system. Clinical and Experimental Neuroimmunology,5(2), 132–136.PubMed
Basdeo, S. A., Kelly, S., O’Connell, K., Tubridy, N., McGuigan, C., & Fletcher, J. M. (2016). Increased expression of Tbet in CD4 + T cells from clinically isolated syndrome patients at high risk of conversion to clinically definite MS. SpringerPlus,5(1), 779.PubMedPubMedCentral
Chen, D., Liu, X., Xia, T., Tekcham, D. S., Wang, W., Chen, H., … Liu, X. (2019). A multidimensional characterization of E3 ubiquitin ligase and substrate interaction network. IScience, 16, 177–191.PubMedPubMedCentral
Cierny, D., Lehotsky, J., Hanysova, S., Michalik, J., Kantorova, E., Sivak, S., … Jesenska, L. (2017). The age at onset in Multiple Sclerosis is associated with patient’s prognosis. Bratislavske Lekarske Listy, 118(6), 374–377.PubMed
Collier, S. P. (2014). TMEVPG1, A Long Noncoding RNA within the Immune System. Vanderbilt University.
Correale, J., Gaitán, M. I., Ysrraelit, M. C., & Fiol, M. P. (2016). Progressive multiple sclerosis: From pathogenic mechanisms to treatment. Brain,140(3), 527–546.
Corvol, J.-C., Pelletier, D., Henry, R. G., Caillier, S. J., Wang, J., Pappas, D., … Oksenberg, J. R. (2008). Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event. Proceedings of the National Academy of Sciences United States of America, 105(33), 11839–11844.
de Andrés, C., Aristimuño, C., de las Heras, V., Martínez-Ginés, M. L., Bartolomé, M., Arroyo, R., … Sánchez-Ramón, S. (2007). Interferon beta-1a therapy enhances CD4 + regulatory T-cell function: An ex vivo and in vitro longitudinal study in relapsing−remitting multiple sclerosis. Journal of Neuroimmunology, 182(1), 204–211.PubMed
de Mello, J. B. H., Cirilo, P. D. R., Michelin, O. C., Domingues, M. A. C., Rudge, M. V. C., Rogatto, S. R., et al. (2017). Genomic profile in gestational and non-gestational choriocarcinomas. Placenta,50, 8–15.PubMed
Dehghanian, F., Kay, M., & Hojati, Z. (2018). Interferon gamma versus beta-interferon in pathogenesis of multiple sclerosis: Battle of two interferons. In A. Minagar (Ed.), Neuroinflammation (pp. 429–448). Amsterdam: Elsevier.
Dendrou, C. A., Fugger, L., & Friese, M. A. (2015). Immunopathology of multiple sclerosis. Nature Reviews Immunology,15(9), 545–558.PubMed
Dolati, S., Marofi, F., Babaloo, Z., Aghebati-Maleki, L., Roshangar, L., Ahmadi, M., … Yousefi, M. (2018). Dysregulated network of mirnas involved in the pathogenesis of multiple sclerosis. Biomedicine & Pharmacotherapy, 104, 280–290.
Driscoll, M. D., Sathya, G., Muyan, M., Klinge, C. M., Hilf, R., & Bambara, R. A. (1998). Sequence requirements for estrogen receptor binding to estrogen response elements. Journal of Biological Chemistry,273(45), 29321–29330.
Ewing, E., Kular, L., Fernandes, S. J., Karathanasis, N., Lagani, V., Ruhrmann, S., … Gomez-Cabrero, D. (2019). Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression. EBioMedicine, 43, 411–423.PubMedPubMedCentral
Farsani, Z. S., Behmanesh, M., & Sahraian, M. A. (2015). Interleukin-10 but not transforming growth factor-β1 gene expression is up-regulated by vitamin D treatment in multiple sclerosis patients. Journal of the Neurological Sciences,350(1), 18–23.PubMed
Gharesouran, J., Taheri, M., Sayad, A., Ghafouri-Fard, S., Mazdeh, M., & Omrani, M. D. (2019). A novel regulatory function of long non-coding RNAs at different levels of gene expression in multiple sclerosis. Journal of Molecular Neuroscience,1, 1–7.
Greer, J. M., & McCombe, P. A. (2011). Role of gender in multiple sclerosis: Clinical effects and potential molecular mechanisms. Journal of Neuroimmunology,234(1), 7–18.PubMed
Haines, J., Stewart, G., Compston, A., Ebers, G., Peltonen, L., D’Alfonso, S., … Eraksoy, M. (2003). A meta-analysis of whole genome linkage screens in multiple sclerosis. Journal of Neuroimmunology, 143(1–2), 39–46.
Hiramatsu, Y., Kitagawa, K., Suzuki, T., Uchida, C., Hattori, T., Kikuchi, H., … Yamamoto, T. (2006). Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination. Cancer Research, 66(17), 8477–8483.PubMed
Kornienko, A. E., Dotter, C. P., Guenzl, P. M., Gisslinger, H., Gisslinger, B., Cleary, C., … Barlow, D. P. (2016). Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology, 17(1), 14.
Korporal, M., Haas, J., Balint, B., Fritzsching, B., Schwarz, A., Moeller, S., … Wildemann, B. (2008). Interferon beta–induced restoration of regulatory T-cell function in multiple sclerosis is prompted by an increase in newly generated naive regulatory T cells. Archives of Neurology, 65(11), 1434–1439.PubMed
Maik-Rachline, G., Hacohen-Lev-Ran, A., & Seger, R. (2019). Nuclear ERK: Mechanism of translocation, substrates, and role in cancer. International Journal of Molecular Sciences,20(5), 1194.PubMedCentral
Mandrekar, J. N. (2010). Receiver operating characteristic curve in diagnostic test assessment. Journal of Thoracic Oncology,5(9), 1315–1316.PubMed
Martins, A. J., Narayanan, M., Prüstel, T., Fixsen, B., Park, K., Gottschalk, R. A., … Wendelsdorf, K. V. (2017). Environment tunes propagation of cell-to-cell variation in the human macrophage gene network. Cell Systems, 4(4), 379–392.PubMedPubMedCentral
McDonald, W. I., Compston, A., Edan, G., Goodkin, D., Hartung, H., Lublin, F. D., … Reingold, S. C. (2001). Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Annals of Neurology, 50(1), 121–127.PubMed
Minagar, A., Ma, W., Zhang, X., Wang, X., Zhang, K., Alexander, J. S., … Albitar, M. (2012). Plasma ubiquitin–proteasome system profile in patients with multiple sclerosis: Correlation with clinical features, neuroimaging, and treatment with interferon-beta-1b. Neurological Research, 34(6), 611–618.PubMed
Mowel, W. K., Kotzin, J. J., McCright, S. J., Neal, V. D., & Henao-Mejia, J. (2018). Control of immune cell homeostasis and function by lncRNAs. Trends in Immunology,39(1), 55–69.PubMed
Naghavi Gargari, B., Behmanesh, M., & Sahraian, M. A. (2015). Effect of vitamin D treatment on interleukin-2 and interleukin-4 genes expression in multiple sclerosis. Physiology and Pharmacology,19(1), 14–21.
Oskooei, V. K., & Ghafouri-Fard, S. (2019). Are long non-coding RNAs involved in the interaction circuit between estrogen receptor and vitamin D receptor? Meta Gene,19, 1–9.
Preedy, V. R., & Patel, V. B. (2015). Biomarkers in cancer. Berlin: Springer.
Qiu, F., Liang, C.-L., Liu, H., Zeng, Y.-Q., Hou, S., Huang, S., … Dai, Z. (2017). Impacts of cigarette smoking on immune responsiveness: Up and down or upside down? Oncotarget, 8(1), 268.
Ratzer, R., Søndergaard, H. B., Christensen, J. R., Börnsen, L., Borup, R., Sørensen, P. S., et al. (2013). Gene expression analysis of relapsing–remitting, primary progressive and secondary progressive multiple sclerosis. Multiple Sclerosis Journal,19(14), 1841–1848.PubMed
Roche, P. J., Hoare, S. A., & Parker, M. G. (1992). A consensus DNA-binding site for the androgen receptor. Molecular Endocrinology,6(12), 2229–2235.PubMed
Sandelin, A., Alkema, W., Engström, P., Wasserman, W. W., & Lenhard, B. (2004). JASPAR: An open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Research,32(suppl_1), D91–D94.PubMedPubMedCentral
Schulze-Topphoff, U., Casazza, S., Varrin-Doyer, M., Pekarek, K., Sobel, R. A., Hauser, S. L., … Baranzini, S. E. (2013). Tob1 plays a critical role in the activation of encephalitogenic T cells in CNS autoimmunity. Journal of Experimental Medicine, 210(7), 1301–1309.PubMedPubMedCentral
Singh, A. J., Ramsey, S. A., Filtz, T. M., & Kioussi, C. (2018). Differential gene regulatory networks in development and disease. Cellular and Molecular Life Sciences,75(6), 1013–1025.PubMed
Spurlock, C. F., III, Tossberg, J. T., Guo, Y., Collier, S. P., Crooke, P. S., III, & Aune, T. M. (2015). Expression and functions of long noncoding RNAs during human T helper cell differentiation. Nature Communications,6, 6932.PubMed
Tzachanis, D., & Boussiotis, V. A. (2009). Tob, a member of the APRO family, regulates immunological quiescence and tumor suppression. Cell Cycle,8(7), 1019–1025.PubMed
Tzachanis, D., Freeman, G. J., Hirano, N., Van Puijenbroek, A. A. F. L., Delfs, M. W., Berezovskaya, A., … Boussiotis, V. A. (2001). Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells. Nature Immunology, 2(12), 1174–1182.PubMed
Tzachanis, D., Lafuente, E. M., Li, L., & Boussiotis, V. A. (2004). Intrinsic and extrinsic regulation of T lymphocyte quiescence. Leukemia & Lymphoma,45(10), 1959–1967.
Tzachanis, D., Li, L., Lafuente, E. M., Berezovskaya, A., Freeman, G. J., & Boussiotis, V. A. (2007). Twisted gastrulation (Tsg) is regulated by Tob and enhances TGF-β signaling in activated T lymphocytes. Blood,109(7), 2944–2952.PubMedPubMedCentral
Ullah, M. F., Ahmad, A., Bhat, S. H., Abu-Duhier, F. M., Barreto, G. E., & Ashraf, G. M. (2019). Impact of sex differences and gender specificity on behavioral characteristics and pathophysiology of neurodegenerative disorders. Neuroscience & Biobehavioral Reviews,102, 95–105.
Wang, D., Qin, H., Du, W., Shen, Y.-W., Lee, W.-H., Riggs, A. D., et al. (2012). Inhibition of S-phase kinase-associated protein 2 (Skp2) reprograms and converts diabetogenic T cells to Foxp3+ regulatory T cells. Proceedings of the National Academy of Sciences USA,109(24), 9493–9498.
Whitacre, C. C., Reingold, S. C., O’looney, P. A., Blankenhorn, E., Brinley, F., Collier, E., … Gilmore, W. (1999). A gender gap in autoimmunity: Task force on gender, multiple sclerosis and autoimmunity. Science, 283(5406), 1277–1278.PubMed
Yao, J., Li, Z., Yang, Z., Xue, H., Chang, H., Zhang, X., … Guo, K. (2018). Long noncoding RNA TOB1-AS1, an epigenetically silenced gene, functioned as a novel tumor suppressor by sponging miR-27b in cervical cancer. American Journal of Cancer Research, 8(8), 1483.
Ysrraelit, M. C., & Correale, J. (2019). Impact of sex hormones on immune function and multiple sclerosis development. Immunology,156(1), 9–22.PubMed
Zastepa, E., Fitz-Gerald, L., Hallett, M., Antel, J., Bar-Or, A., Baranzini, S., … Haegert, D. G. (2014). Naive CD4 T-cell activation identifies MS patients having rapid transition to progressive MS. Neurology, 82(8), 681–690.PubMedPubMedCentral
Metadata
Title
The Putative Association of TOB1-AS1 Long Non-coding RNA with Immune Tolerance: A Study on Multiple Sclerosis Patients
Authors
Reyhaneh Dehghanzad
Majid Pahlevan Kakhki
Asieh Alikhah
Mohammad Ali Sahraian
Mehrdad Behmanesh
Publication date
01-03-2020
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 1/2020
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-019-08567-1

Other articles of this Issue 1/2020

NeuroMolecular Medicine 1/2020 Go to the issue

Original Paper

Prolactin is Not Associated with Disability and Clinical Forms in Patients with Multiple Sclerosis

Original Paper

Variation in DNA Repair System Gene as an Additional Modifier of Age at Onset in Spinocerebellar Ataxia Type 3/Machado–Joseph Disease

Original Paper

Butanol Extract of Tinospora cordifolia Ameliorates Cognitive Deficits Associated with Glutamate-Induced Excitotoxicity: A Mechanistic Study Using Hippocampal Neurons

Original Paper

C1 Esterase Inhibitor Reduces BBB Leakage and Apoptosis in the Hypoxic Developing Mouse Brain

Original Paper

Intravenous Immunoglobulin (IVIg) Induce a Protective Phenotype in Microglia Preventing Neuronal Cell Death in Ischaemic Stroke

Original Paper

CSF sAPPα and sAPPβ levels in Alzheimer’s Disease and Multiple Other Neurodegenerative Diseases: A Network Meta-Analysis