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Rheumatoid arthritis fibroblast-like synoviocytes maintain tumor-like biological characteristics through ciRS-7-dependent regulation of miR-7

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Abstract

Background

Altered phenotype of Fibroblast-like synoviocyte(FLS) is an important cause of the pathogenesis and progression of rheumatoid arthritis(RA), but the specific mechanism causing this change has not yet been fully explained. The exact mechanism by which the biological properties of FLS change in RA is still unclear. microRNAs (miRNAs) have been shown to affect changes in the biological properties of RA-FLS, but the critical miRNAs remain to be discovered. Thus, we first used miRNA microarray and WGCNA to confirm the RA-FLS miRNA landscape and establish their biological functions via network analyses at the system level, as well as to provide a platform for modulating the overall phenotypic effects of RA-FLS.

Methods

We enrolled a total of 3 patients with RA and 3 healthy participants, constructed a network analysis of via miRNA microarray and RNA-sequencing. Furthermore, the coexpression analyses of miR-7 and ciRS-7 were verified by siRNA transfection, overexpression and qPCR analyses. Finally, we evaluated the effects of adjusting the expression levels of miR-7 and ciRS-7 on RA-FLS, respectively.

Results

We identified distinct miRNA features in RA-FLS, including miR-7, which was significantly lower expressed. Furthermore, we discovered the negative regulatory relationship between ciRS-7 and miR-7 in RA-FLS. Finally, we overexpressed miR-7 in RA-FLS and discovered that miR-7 inhibited RA-FLS hyperproliferation, migration, invasion, and apoptosis, whereas ciRS-7 overexpression reversed these effects.

Conclusions

The results indicate that the dysregulation of miR-7 in FLS may be involved in the pathological processes of RA and that ciRS-7 induced the suppression of tumor-like biological characters of RA-FLS via modulation of miR-7. These findings help us understand the essential roles of a regulatory interaction between ciRS-7 and miR-7 mediating disease activity of RA, and will facilitate to develop potential intervention target for RA.

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Funding

This work was supported by grants provided from the National Natural Science Foundation of China (No. 81771750).

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Authors and Affiliations

  1. Division of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, No.600, Tianhe Road, Tianhe District, 51000, Guangzhou City, China

    Zuoyu Hu MPhil, Jingrong Chen PhD, Weizhen Weng MD, Ye Chen PhD & Yunfeng Pan MD

  2. Center for Clinical Immunology, The Third Affiliated Hospital of Sun Yat-sen University, No.600, Tianhe Road, Tianhe District, 51000, Guangzhou City, China

    Jingrong Chen PhD & Ye Chen PhD

  3. Medical Research Center, The Eighth Affiliated Hospital, Sun Yat-sen University, 518033, Shenzhen, China

    Manli Wang MD

Authors
  1. Zuoyu Hu MPhil
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  2. Jingrong Chen PhD
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  3. Manli Wang MD
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  4. Weizhen Weng MD
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  5. Ye Chen PhD
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  6. Yunfeng Pan MD
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yunfeng Pan, Zuoyu Hu and Manli Wang. The first draft of the manuscript was written by Jingrong Chen, Weizhen Weng and Ye Chen. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yunfeng Pan MD.

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The authors declare no conflicts of interest.

Ethics Approval

The research was approved by the ethics committee of the Third Affiliated Hospital at the Sun Yat-sen University and all subjects were given the written informed consent in accordance with the Declaration of Helsinki. The Ethics board approval number is [2020]02–090.

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Hu, Z., Chen, J., Wang, M. et al. Rheumatoid arthritis fibroblast-like synoviocytes maintain tumor-like biological characteristics through ciRS-7-dependent regulation of miR-7. Mol Biol Rep 49, 8473–8483 (2022). https://doi.org/10.1007/s11033-022-07666-w

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  • DOI: https://doi.org/10.1007/s11033-022-07666-w

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