Dataset Information

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 the renal tissues of patients with LN (P =?0.014). Bio-informatics 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-?1 (TGF-?1), 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.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7805051 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Zhang Chunyi C Gao Congcong C Di Xueqi X Cui Siwan S Liang Wenfang W Sun Wenbo W Yao Menghui M Liu Shengyun S Zheng Zhaohui Z

Arthritis research & therapy 20210113 1

<h4>Background</h4>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.<h4>Method ...[more]

PMID: 33436040

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Project description:Objective:To explore the regulatory effects of circZNF609 on proliferative and migratory capacities of gastric cancer (GC) and its underlying mechanism. Methods:Expression level of circZNF609, CDK6 and miR-483-3p in GC tissues and cells were detected qRT-PCR verification. CCK-8 and transwell assay were conducted the cell viability and migratory capacities of GC cells. Dual luciferase assay was enrolled to confirm the interaction among circZNF609, CDK6 and miR-483-3p. Western blot was used to detect the protein level of CDK6. Results:Expression levels of circZNF609 were higher in GC patients by qRT-PCR.GC patients with higher expression of circZNF609 were expected to have a higher TNM stage and lower 5-year survival than those with lower expression. ROC curves showed a well diagnostic value of circZNF609 in GC. Treatment of RNase R in GC cells downregulated the expression of ZNF609, whereas circZNF609 expression did not change. Furthermore, cytoplasmic expression of circZNF609 was higher than those of nuclear expression. Besides, biological experiments indicated that overexpression of circZNF609 promoted the proliferative and migratory capacities of GC cells. To demonstrate the underlying mechanism of circZNF609, we found that circZNF609 bound to miR-483-3p, which presented a lower expression in GC tissues than that of paracancerous tissues. Both circZNF609 and miR-483-3p could bind to Ago2, suggesting that circZNF609 may act as a sponge of miR-483-3p. In addition, the effect of overexpressed circZNF609 on cellular behaviors of GC cells were partly reversed by overexpression of miR-483-3p. Bioinformatics suggested that CDK6 has a potential binding site with miR-483-3p. The expression of CDK6 markedly increased in GC tissues and cells, which was negatively correlated with miR-483-3p expression. Dual-luciferase reporter gene results indicated that miR-483-3p could bind to the 3'-UTR of CDK6. Moreover, miR-483-3p downregulated CDK6 at both mRNA and protein levels. Overexpression of miR-483-3p inhibited proliferative and migratory capacities of GC cells, which were reversed by CDK6 overexpression. Conclusion:In summary, the expression of circZNF609 is upregulated in GC. CircZNF609 can be used as the sponge of miR-483-3p to regulate the expression level of CDK6, thus participating in the progression of GC by regulating the proliferative and migratory capacities of GC cells.

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Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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