Background: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs(circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases, such as, autoimmunity diseases. However, the role of circRNA in lupus nephritis has been rarely reported.

Objectives: In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN.

Methods: Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by RNA sequencing (RNA-seq). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Correlation analysis and receiver operating characteristic (ROC) curve were used to reveal the clinical value of selected circRNA, miRNA and mRNA. The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The degrees of renal fibrosis between the two groups were compared by Masson-trichome staining and immunohistochemistry staining.

Results: 159 circRNAs were significantly dysregulated in LN patients compared with NC group. The expression of hsa_circ_0123190 was significantly decreased in renal tissues of patients with LN (p=0.014), as same as the sequencing results. The area under the ROC curve of hsa_circ_0123190 in renal tissues was 0.820. Bio-informatic analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p which was also validated to interact with APLNR mRNA. APLNR mRNA expression was positively related with chronicity index (CI) of LN (R²=0.452, p=0.033). Finally, the factors of renal fibrosis, especially TGF-β (p=0.018), were more pronounced in the LN group.

Conclusion: Hsa_circ_0123190 could function as a ceRNA to regulate APLNR expression involved in renal fibrosis by sponging hsa-miR-483-3p in LN

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Disclosure of Interests: None declared