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MicroRNA-133 suppresses cell viability and migration of rheumatoid arthritis fibroblast-like synoviocytes by down-regulation of MET, EGFR, and FSCN1 expression

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Abstract

Aberrant proliferation and migration of fibroblast-like synoviocytes (FLS) are major characteristics of rheumatoid arthritis (RA). MicroRNA-133 (miR-133) is a tumor-suppressive miRNA that targets various genes responsive for cell proliferation and migration. The aim of this study was to examine the effect of miR-133 on RA FLS. A high throughput miRNA microarray was performed in synovium from mice with collagen-induced arthritis (CIA). Expression levels of miR-133 and the putative targets were determined in synovium and FLS from patients with RA and mice with CIA. Overexpression of miR-133 in RA FLS was performed by lentiviral vector-mediated transfer of precursor miRNA (pre-miR). The expression of miR-133a/b was decreased in the joint tissue and FLS of CIA mice, as determined by miRNA array and qRT-PCR. Down-regulation of miR-133a/b expression could also be observed in synovium and FLS from patients with RA. Overexpression of miR-133 reduced cell viability and migration of RA FLS, with decreased levels of FSCN1, EGFR, and MET. Our findings demonstrated the inhibitory effects of miR-133 on FLS viability and migration, and might contribute to the pharmacologic development of miR-133 therapeutics in patients with RA.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

RA:

Rheumatoid arthritis

CIA:

Collagen-induced arthritis

FLS:

Fibroblast-like synoviocytes

MiRNA:

MicroRNA

MicroRNA-133:

MiR-133

Precursor miRNA:

Pre-miR

EMT:

Epithelial-mesenchymal transition

UTR:

Untranslated region

ESCC:

Esophageal squamous cell carcinoma

GEO:

Gene Expression Omnibus

CIA FLS:

FLS from mice with CIA

RA FLS:

FLS from patients with RA

N FLS:

FLS from naïve control mice

H FLS:

FLS from healthy human FLS

TNF:

Tumor necrosis factor

MOI:

Multiplicity of infection

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Acknowledgements

We thank Dr. D. Trono (Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland) for generously providing psPAX2 and pMD2.G plasmids for the production of lentiviral vectors and the Laboratory Animal Center, College of Medicine, National Cheng Kung University and Taiwan Animal Consortium (AAALAC International Full Accreditation) for the animal care. We also thank professor Chi-Chien Lin helps us collect synovial tissue samples at Taichung Veterans General Hospital, Taichung, Taiwan.

Funding

This work was supported by MOST 108-2314-B-006-037-MY3, and 108-2314-B-273-005-MY3 from the Ministry of Science and Technology, Taiwan.

Author information

Author notes

  1. Shih-Yao Chen, Jeng-Long Hsieh, and Po-Ting Wu have contributed equally to this work.

Authors and Affiliations

  1. Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, 89, Wenhua 1st street, Tainan, 71703, Taiwan

    Shih-Yao Chen & Jeng-Long Hsieh

  2. Department of Orthopaedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Po-Ting Wu

  3. Department of Orthopaedics, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Po-Ting Wu

  4. Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan

    Po-Ting Wu

  5. Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan

    Po-Ting Wu

  6. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Ai-Li Shiau

  7. Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, 539, Zhongxiao Road, Chiayi, 60002, Taiwan

    Ai-Li Shiau & Chao-Liang Wu

  8. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Chao-Liang Wu

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Contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and approved the final version to be published. Drs. CLWu and Chen have full access to all of the data in the study, and take responsibility for the integrity of data and the accuracy of data analysis. Conceptualization: SYC, JLH, PTW, CLW. Data curation: SYC, JLH, PTW, ALS, CLW. Formal Analysis: SYC, JLH, PTW, ALS, CLW. Funding acquisition: SYC, JLH. Investigation: SYC, JLH, PTW, CLW. Methodology: SYC, JLH, PTW, ALS, CLW. Project administration: SYC, JLH. Resources: SYC, JLH, PTW, CLW. Supervision: SYC, JLH, PTW, CLW. Validation: SYC, JLH, PTW, CLW. Visualization: SYC, JLH, CLW. Writing-original draft: SYC, JLH, CLW. Writing-review and editing: SYC, JLH, PTW, ALS, CLW.

Corresponding authors

Correspondence to Shih-Yao Chen or Chao-Liang Wu.

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Chen, SY., Hsieh, JL., Wu, PT. et al. MicroRNA-133 suppresses cell viability and migration of rheumatoid arthritis fibroblast-like synoviocytes by down-regulation of MET, EGFR, and FSCN1 expression. Mol Cell Biochem 477, 2529–2537 (2022). https://doi.org/10.1007/s11010-022-04457-6

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