Hsa_circ_0044235 regulates the pyroptosis of rheumatoid arthritis via MiR-135b-5p-SIRT1 axis

• Published in: Cell cycle (Georgetown, Tex.) Vol. 20; no. 12; pp. 1107 - 1121
• Main Authors: Chen, Shaojian, Luo, Zhihuan, Chen, Xiaguang
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 18.06.2021
• Subjects: Animals; Apoptosis - genetics; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - genetics; Case-Control Studies; Cell Proliferation - genetics; Cells, Cultured; Cytokines - metabolism; Disease Models, Animal; Hsa_circ_0044235; Humans; Male; Mice; Mice, Inbred DBA; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; pyroptosis; Pyroptosis - genetics; Research Paper; rheumatoid arthritis; RNA, Circular - blood; RNA, Circular - genetics; Signal Transduction - genetics; Sirtuin 1 - blood; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Synoviocytes - metabolism; Transfection; Hsa_circ_0044235; pyroptosis; rheumatoid arthritis
• ISSN: 1538-4101; 1551-4005; 1551-4005
• DOI: 10.1080/15384101.2021.1916272

Studies have found that cell pyroptosis is involved in the occurrence and development of rheumatoid arthritis (RA). Hsa_circ_0044235 has been found to be significantly low-expressed in RA patients. The purpose of this research was to reveal the regulatory mechanism of hsa_circ_0044235 in the pyroptosis pathway of RA. Serum expressions of hsa_circ_0044235 and SIRT were detected by RT-qPCR, and the relationship of the two genes was analyzed by Pearson. Next, a collagen-induced arthritis (CIA) mouse model was constructed to examine the effect of hsa_circ_0044235 on knee joint injury. The number of apoptotic cells and the level of inflammatory cytokines in synovial tissue were detected by TUNEL and ELISA. Fibroblast-like synoviocytes (FLSs) were extracted as in vitro study subject. Functional assays including flow cytometry and immunofluorescence staining, molecular experiments including RT-qPCR, Western blot and dual luciferase assay, and bioinformatics analysis were performed to analyze the mechanism of hsa_circ_0044235 in pyroptosis in FLSs. Hsa_circ_0044235 and SIRT1 expressions were suppressed in RA patients and the two were positively correlated. Overexpressed hsa_circ_0044235 attenuated joint inflammation, cell apoptosis, and joint damage, reduced foot pad thickness, clinical case scores, inhibited the NLRP3-mediated pyroptosis pathway but promoted SIRT1 expression in CIA mice. Overexpressed hsa_circ_0044235 inhibited caspase-1 content and the NLRP3-mediated pyroptosis pathway. Moreover, hsa_circ_0044235 promoted SIRT1 expression by sponging miR-135b-5p in FLSs. Additionally, the effect of overexpressed hsa_circ_0044235 on FLSs was reversed by miR-135b-5p mimic and siSIRT1, while the effect of siSIRT1 was reversed by miR-135b-5p inhibitor. Hsa_circ_0044235 regulated NLRP3-mediated pyroptosis through miR-135b-5p-SIRT1 axis to regulate the development of RA.