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

ABSTRACT

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)-1β, 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.

KEYWORDS:

• Periodontitis
• human gingival fibroblasts
• pyroptosis
• circ_0138959
• miR-527
• CASP5

Highlights

1. Knockdown of circ_0138959 suppresses pyroptosis of HGFs.

2. Circ_0138959 sponges miR-527 in HGFs.

3. Upregulation of miR-527 reverses the effects of circ_0138959 in HGFs.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Authors’ contributions

All authors participated in the design, interpretation of the studies, and analysis of the data and review of the manuscript. JX P drafted the work and revised it critically for important intellectual content; L Z and J L were responsible for the acquisition, analysis, and interpretation of data for the work; and GY W made substantial contributions to the conception and design of the work.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.