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The circRNA–miRNA–mRNA regulatory network in plasma and peripheral blood mononuclear cells and the potential associations with the pathogenesis of systemic lupus erythematosus

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Abstract

Objectives

This study aimed to explore the possible role of plasma and peripheral blood mononuclear cells (PBMCs) circular RNA (circRNA) in systemic lupus erythematosus (SLE).

Method

Total RNA was extracted from blood plasma samples obtained from 10 patients with SLE and 10 healthy controls and subjected to microarray analysis to define the profile of circRNA expression. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) amplification was conducted. The overlapped circRNA between PBMCs and plasma was performed, the interactions with microRNAs were predicted, the miRNA target mRNA was predicted, and the GEO database was used. The Gene ontology and pathway analysis was performed.

Results

One hundred thirty-one upregulated and 314 significantly downregulated circRNAs were identified in the plasma of patients with SLE by the Fold change criteria (≥ 2.0) and P < 0.05. The qRT-PCR results showed that the expression of has-circRNA-102531, has-circRNA-103984, and has-circRNA-104262 was increased in plasma of SLE, and the expression of has-circRNA-102972, has-circRNA-102006, has-circRNA-104313 was decreased in plasma of SLE. Twenty-eight upregulated circRNAs and 119 downregulated circRNAs were overlapped from PBMCs and plasma, and ubiquitination was enriched. Furthermore, the circRNA-miRNA-mRNA network was constructed in SLE after analyzing dataset GSE61635 from GEO. The circRNA-miRNA-mRNA network comprises 54 circRNAs, 41 miRNAs, and 580 mRNAs. In addition, the TNF signaling pathway and the MAPK pathway were enriched from the mRNA of the miRNA target.

Conclusion

We first revealed the differentially expressed circRNAs in plasma and PBMCs, and then the circRNA-miRNA-mRNA network was constructed. The network’s circRNAs could be a potential diagnostic biomarker and potentially play an important role in the pathogenesis and development of SLE.

Key Points

• This study analyzed the circRNAs expression profiles combined with the plasma and PBMCs, which provided a comprehensive overview of circRNAs expression patterns in SLE.

• The network of the circRNA-miRNA-mRNA in SLE was constructed, which contributes to a better understanding of the pathogenesis and development of SLE.

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Funding

This project was supported by Shenzhen science and technology innovation commission (No. JCYJ20200109140412476), the National Natural Science Foundation of China (82100726), and the Shenzhen Science and Technology Innovation Commission Basic Research Program (JCYJ20210324110403011), Guangdong Basic and Applied Basic Research Foundation (2020A1515110970). “San-ming” Project of Medicine in Shenzhen (no.SZSM201812097).

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Authors and Affiliations

  1. Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China

    Fengping Zheng, Lishan Tan, Fan Zhang, Sanmu Li, Zhiwei Lai & Zuying Xiong

  2. Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, Guangdong, 518020, People’s Republic of China

    Huixuan Xu & Yong Dai

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  1. Fengping Zheng
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Correspondence to Zuying Xiong or Yong Dai.

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ESM 1

Fig. S1 The GO results of these dysregulated mRNAs. Fig. S2 The KEGG pathway results of these dysregulated mRNAs. Fig. S3 A network of overlapped upregulated gene’s interaction

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Zheng, F., Tan, L., Zhang, F. et al. The circRNA–miRNA–mRNA regulatory network in plasma and peripheral blood mononuclear cells and the potential associations with the pathogenesis of systemic lupus erythematosus. Clin Rheumatol 42, 1885–1896 (2023). https://doi.org/10.1007/s10067-023-06560-5

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