Inhibition of circular RNA circ_0138959 alleviates pyroptosis of human gingival fibroblasts via the microRNA-527/caspase-5 axis

Circular RNA (circRNA) plays a regulatory role in periodontitis. This study explored whether circ_0138959 affected lipopolysaccharide (LPS)-induced pyroptosis in human gingival fibroblasts (HGFs). The periodontal ligament (PDL) tissues and HGFs were derived from patients with periodontitis and healthy volunteers. HGFs treated with LPS were considered to mimic periodontitis in vitro. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the mRNA expression levels of circRNAs, miR-527, and caspase-5 (CASP5), and Western blotting assay was used to measure protein expression levels of caspase-1, caspase-4, and cleaved N-terminal gasdermin D (GSDMD-N). Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The concentration of lactate dehydrogenase (LDH), interleukin (IL)-1 beta, and IL-18 and the pyroptosis rate were determined to evaluate pyroptosis. The interaction between miR-527 and circ_0138959 or CASP5 was verified by dual-luciferase reporter and RNA pull-down assays. Circ_0138959 expression was higher in the PDL tissues of patients with periodontitis than in the healthy group; likewise, circ_0138959 was also upregulated in LPS-treated HGFs. Suppressed circ_0138959 increased cell viability and decreased pyroptosis of HGFs induced by LPS. miR-527 was a target of circ_0138959, and inhibition of miR-527 contributed to the dysfunction of LPS-treated HGFs and reversed the protective effects of downregulated circ_0138959. Additionally, miR-527 targeted CASP5. Increased CASP5 abrogated the effects of overexpressed miR-527 on cell viability and pyroptosis of LPS-treated HGFs. Inhibition of circ_0138959 promoted cell viability and suppressed pyroptosis of HGFs via the miR-527/CASP5 axis. Therefore, knockdown of circ_0138959 may be a promising therapy for periodontitis.

Automated summary

This study found that circ_0138959 is upregulated in periodontitis and plays a regulatory role in LPS-induced pyroptosis. miR-527 is a target of circ_0138959 and its inhibition results in dysfunction of HGFs and reverses the protective effects of downregulated circ_0138959. CASP5 is a target gene of miR-527 and its overexpression abolishes the effects of miR-527 on HGFs. Inhibition of circ_0138959 promotes cell viability and suppresses pyroptosis of HGFs through the miR-527/CASP5 axis.