CircSMURF2 alleviates cell apoptosis by binding DIABLO promote ubiquitination and its expression level and clinical significance in lupus nephritis

Background

Lupus nephritis (LN) is an autoimmune disease that affects kidneys and is considered one of the most prevalent complications of systemic lupus erythematosus (SLE). We screened differentially expressed circRNAs through circRNA sequencing in peripheral blood molecular cells (PBMC) of LN patients and verified that circSMURF2 was downregulated  and its correlation with laboratory indicators.

Our study reveals for the first time that circSMURF2 was downregulated in LN patients and mediated cell apoptosis in HK2s by modulating DIABLO ubiquitination.

Methods

The expression and function of circSMURF2 were detected by qRT-PCR and FISH. The interactions between circSMURF2 and DIABLO were analyzed by RNA pull-down assay, Mass Spectrometry and RNA Immunoprecipitation. HK2s treated with lentivirus overexpression of circSMURF2 was applied for  experiments.

Result

Functionally, circSMURF2 promoted proliferation and inhibited apoptosis in Human renal cortex proximal tubule epithelial cells (HK2). Mechanistically, circRNA pull-down analysis showed that circSMURF2 functions in HK2s by binding to DIABLO protein and negatively regulating its expression through accelerating its ubiquitination.