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MiR-320a is Downregulated in Patients with Myasthenia Gravis and Modulates Inflammatory Cytokines Production by Targeting Mitogen-activated Protein Kinase 1

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Abstract

Myasthenia gravis (MG) are T-cell dependent antibody-mediated autoimmune disorders, microRNAs are important regulators of human autoimmune disease pathogenesis. Here, we investigated the miRNAs expression profiles in MG for the first time and found that miR-320a was significantly downregulated in MG patients compared to normal healthy people. Meanwhile, pro-inflammatory cytokins in MG patients were overexpressed. Furthermore, we identified MAPK1 as a direct target of miR-320a. Downregulation of miR-320a induced the overexpression of pro-inflammatory cytokins through promoting COX-2 expression. This process was modulated by ERK/ NF-κB pathways. Taken together, our findings suggested that miR-320a could play a role in modulation of inflammatory cytokins production.

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Abbreviations

MG:

Myasthenia gravis

MAPK1:

Mitogen-activated protein kinase1

3′UTR:

3′untranslated region

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

PBMCs:

Peripheral blood mononuclear cell

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Acknowledgments

This work was supported by Shanghai Science and Technology Commission (No. 10JC1414500) and the Shanghai Committee of Science and Technology [grant 11DZ2260600].

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China

    Zhuoan Cheng, Lin Jiang, Anle Zhang & Jianwen Liu

  2. Longhua Hospital Affiliated to Shanghai University of traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China

    Shaobo Qiu & Ping Liu

  3. The China Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Liaoning, 110032, People’s Republic of China

    Wenjing Bao

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  1. Zhuoan Cheng
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  2. Shaobo Qiu
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  3. Lin Jiang
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  4. Anle Zhang
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  6. Ping Liu
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  7. Jianwen Liu
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Corresponding authors

Correspondence to Ping Liu or Jianwen Liu.

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Online Resource 1

MiR-486-5p (A) and miR-363(B) expression differentiate 34 MG patients from 10 normal control by real-time PCR (JPEG 24 kb)

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Online Resource 2

The bioinformatic analysis data by targetscan database (available at http://www.targetscan.org/) (JPEG 25 kb)

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Cheng, Z., Qiu, S., Jiang, L. et al. MiR-320a is Downregulated in Patients with Myasthenia Gravis and Modulates Inflammatory Cytokines Production by Targeting Mitogen-activated Protein Kinase 1. J Clin Immunol 33, 567–576 (2013). https://doi.org/10.1007/s10875-012-9834-5

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  • DOI: https://doi.org/10.1007/s10875-012-9834-5

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