A novel circRNA, circRACGAP1, hampers the progression of systemic lupus erythematosus via miR-22-3p-mediated AKT signalling

Abstract

Background

Systemic lupus erythematosus (SLE) is defined as a multisystem autoimmune disease involving various organs, of which exact molecular mechanisms remain elusive. Here, we aimed to investigate a novel circular RNA (circRNA), circRACGAP1, abnormally expressed in SLE and explored its underlying regulatory network.

Methods

The expression patterns of circRACGAP1 were determined in patients diagnosed with SLE by using a qRT-PCR assay. Spearman correlation analysis was employed to evaluate the correlation between circRACGAP1 and clinicopathological variables in patients with SLE. Flow cytometry and TUNEL assays were subjected to assess the cell apoptosis. Nuclear-cytoplasmic fractionation and luciferase reporter assay was used to verify the circRACGAP1/miR-22-3p/PTEN axis. Western blot analysis was performed to measure the PTEN/AKT signalling-related proteins and apoptotic-related biomarkers.

Results

Down-regulated circRACGAP1 was observed and correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, anti-double-stranded (ds) DNA, and complement C3 level in patients with SLE. Overexpression of circRACGAP1 significantly alleviated cell apoptosis in Jurkat cells within UVB exposure. Mechanistic investigation revealed that circRACGAP1 could serve as a sponge of miR-22-3p to regulate PTEN/AKT signalling.

Conclusions

Collectively, circRACGAP1 regulated the AKT signalling pathway via binding to miR-22-3p in the progression of SLE, suggesting therapeutic targets for SLE treatment.

Keywords:

• Systemic lupus erythematosus
• circRACGAP1
• miR-22-3p
• PTEN
• AKT signalling

Authors' contributions

Han-Ying Mei: conception and design of the work. Ju Liu, Xiao-Ping Shen: data acquisition, drafting the work. Han-Ying Mei, Rui Wu: data analysis and data interpretation, revising it critically for important intellectual content.

Disclosure statement

The authors declare that there are no conflicts of interest.

Funding

This work was supported by The science and technology program of Jiangxi Provincial Health Commission: Analysis on the correlation between lipomics and prognosis of different subtypes of antiphospholipid syndrome (No.SKJP_220219110).