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Potential Biomarker and Therapeutic LncRNAs in Multiple Sclerosis Through Targeting Memory B Cells

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Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease that degenerates the central nervous system (CNS). B cells exacerbate the progression of CNS lesions in MS by producing auto-antibodies, pro-inflammatory cytokines, and presenting auto-antigens to activated T cells. Long non-coding RNAs (lncRNAs) play a crucial role in complex biological processes and their stability in body fluids combined with their tissue specificity make these biomolecules promising biomarker candidates for MS diagnosis. In the current study, we investigated memory B cell-specific lncRNAs located, on average, less than 50 kb from differentially expressed protein-coding genes in MS patients compared to healthy individuals. Moreover, we included in our selection criteria lncRNA transcripts predicted to interact with microRNAs with established involvement in MS. To assess the expression levels of lncRNAs and their adjacent protein-coding genes, quantitative reverse transcription PCR was performed on peripheral blood mononuclear cells samples of 50 MS patients compared to 25 controls. Our results showed that in relapsing MS patients, compared to remitting MS patients and healthy controls, lncRNA RP11-530C5.1 was up-regulated while AL928742.12 was down-regulated. Pearson’s correlation tests showed positive correlations between the expression levels of RP11-530C5.1 and AL928742.12 with PAWR and IGHA2, respectively. The results of the ROC curve test demonstrated the potential biomarker roles of AL928742.12 and RP11-530C5.1. We conclude that these lncRNAs are potential markers for detection of relapsing MS patients.

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Abbreviations

cDNA:

Complementary DNA

CNS:

Central nervous system

DNase I:

Deoxyribonuclease I

EDSS:

Expanded disability status scale

GEO:

Gene expression omnibus

GSE:

GEO series

IGHA2 :

Immunoglobulin heavy constant alpha 2

EDTA:

Ethylenediaminetetraacetic acid

lncRNA:

Long non-coding RNA

miRNA:

microRNA

MS:

Multiple sclerosis

PAWR :

PRKC apoptosis WT1 regulator

PBMC:

Peripheral blood mononuclear cell

RT-qPCR:

Quantitative reverse transcription PCR

ROC curve:

Receiver operating characteristic

RRMS:

Relapsing-remitting multiple sclerosis

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Acknowledgements

The authors declare that they have no competing interests. A part of this project was supported by the National Institute for Medical Research Development (NIMAD’s Project No. 942792) and also partly by Royan Institute for Biotechnology.

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Author notes

  1. Shohreh Teimuri

    Present address: Institute of Cell Biology, University of Bern, Bern, Switzerland

  2. Aref Hosseini

    Present address: Institute of Biochemistry and Molecular Medicine, NCCR TransCure, University of Bern, Bern, Switzerland

Authors and Affiliations

  1. Department of Biology, Hakim Sabzevari University, Sabzevar, Iran

    Elahe Ghoveud & Jafar Vatandoost

  2. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

    Shohreh Teimuri & Kamran Ghaedi

  3. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Royan St., Salman St., Khorsagan, Isfahan, 816513-1378, Iran

    Aref Hosseini, Kamran Ghaedi & Mohammad Hossein Nasr Esfahani

  4. Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Masood Etemadifar

  5. Department of Biomedical Sciences, Florida State University College of Medicine, West Call Street, Tallahassee, FL, 32306-4300, USA

    Timothy L. Megraw

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Ghoveud, E., Teimuri, S., Vatandoost, J. et al. Potential Biomarker and Therapeutic LncRNAs in Multiple Sclerosis Through Targeting Memory B Cells. Neuromol Med 22, 111–120 (2020). https://doi.org/10.1007/s12017-019-08570-6

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