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Analysis of microRNA-199a-3p expression in CD4+ T cells of systemic lupus erythematosus

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Abstract

Objectives

Accumulating evidence have suggested microRNAs (miRNAs) play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Here we aimed to explore aberrant expression of miRNAs in CD4+ T cells from SLE patients and their potential function in SLE pathogenesis.

Methods

First, next-generation sequencing was performed on CD4+ T cells from four SLE patients and three healthy controls (HCs). Candidate miRNAs were then validated in CD4+ T cells from 97 patients with SLE, 16 patients with rheumatoid arthritis, and 12 HCs using qRT-PCR. Then the relationship between the candidate miRNA and clinical characteristics was analyzed. Bioinformatics analysis and validation of the target genes of the candidate miRNA were performed.

Results

A total of 66 upregulated miRNAs and 70 downregulated miRNAs were found between SLE and normal CD4+ T cells samples. miR-199a-3p was identified significant upregulation in the CD4+ T cells of lupus patients. High expression of miR-199a-3p was correlated with several clinical characteristics including low C3 level, positive anti-dsDNA antibody, high ESR level, active lupus nephritis, and active disease activity. When distinguishing active LN from non-LN or active lupus from stable lupus, the AUCs of miR-199a-3p were 0.68 and 0.70, respectively. And the expression of miR-199a-3p, involved in JAK-STAT signaling pathway, was negatively correlated with the STAM expression in CD4+ T cells of SLE.

Conclusion

Our study suggested a novel and promising role of miR-199a-3p in CD4+ T cells for SLE. Further studies are needed to precisely determine the function of miR-199a-3p in this disease.

Key Points

• Aberrant expression of miRNAs in CD4+ T cells and their potential function in SLE pathogenesis remained unclear.

• miR-199a-3p in CD4+ T cells plays a novel role in the pathogenesis of SLE and serves as a potential target for SLE.

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Data availability

All data generated or analyzed in this study are included in this article and its Supplementary materials.

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Acknowledgements

We thank all patients and healthy donors who participated in this study.

Funding

This research was supported by the Clinical Research Plan of SHDC (SHDC2020CR1015B) to YS and Cultivating Funds of Renji Hospital South Campus, Shanghai Jiaotong University School of Medicine (2016PWGZR05) to GG.

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Author notes

  1. Guannan Geng and Huijing Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Huijing Wang, Guannan Geng, Danting Zhang & Shuang Ye

  2. Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Institute of Nephrology, Zhejiang University, Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China

    Huijing Wang & Fei Han

  3. Gene Editing Core Facility, Center for Excellence in Brain Science and intelligence Technology, Chinese Academy of Sciences, Shanghai, China

    Guannan Geng

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  1. Huijing Wang
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Contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Ye had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. WH, YS.

Acquisition of data. WH, GG, ZD, HF.

Analysis and interpretation of data. WH, GG, YS.

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Correspondence to Shuang Ye.

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The research protocol was approved by the Renji Hospital of Shanghai Jiaotong University School of Medicine. All subjects who participated in this study provided written informed consent.

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Wang, H., Geng, G., Zhang, D. et al. Analysis of microRNA-199a-3p expression in CD4+ T cells of systemic lupus erythematosus. Clin Rheumatol 42, 1683–1694 (2023). https://doi.org/10.1007/s10067-023-06534-7

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