Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis

Abstract

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. However, the role of circRNA in lupus nephritis has been rarely reported. 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 next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining. Results 159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in renal tissues of patients with LN (P = 0.014). 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. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-β1 (TGF-β1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018). Conclusion Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.

miR-483-3p targets FGFR2 to inhibit cardiomyocyte pyroptosis NLRP3/Caspase-1/GSDMD signaling axis and reduce myocardial fibrosis

“…Fernandez EJ found in vitro that overexpression of miR-483-3p can reduce in ammatory response and reduce damage to human aortic endothelial cells [14]; Teng L showed that miR-483-3p mediates the regulation of LncRNA MALAT1 in the expression of hypersensitivity C-reactive protein, a marker of in ammation [15]. miR-483-3p also plays a very important role in the regulation of brotic diseases [15][16][17]. However, the role and mechanism of miR-483-3p in MF remains unclear.…”