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Circular RNAs (circRNAs) have been demonstrated to play crucial roles in the development and progression of many diseases, including rheumatoid arthritis (RA). However, the functions and molecular mechanism of circ_0008360 in RA remain unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ_0008360, microRNA-135b-5p (miR-135b-5p), and histone deacetylase 4 (HDAC4). Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and flow cytometry analysis were performed to assess cell proliferation, migration, and apoptosis, respectively. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). The interaction between miR-135b-5p and circ_0008360 or HDAC4 was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) and RNA pull-down assays. Western blot assay was used to detect the protein expression of HDAC4 and proliferating cell nuclear antigen (PCNA). The expression of circ_0008360 was downregulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0008360 suppressed the proliferation, migration, and inflammation and promoted apoptosis of RA-FLSs, and circ_0008360 knockdown showed opposite effects. Moreover, miR-135b-5p was a direct target of circ_0008360, and miR-135b-5p could reverse the effects of circ_0008360 on proliferation, migration, inflammation, and apoptosis in RA-FLSs. Furthermore, HDAC4 was a downstream target of miR-135b-5p, and miR-135b-5p accelerated the proliferation, migration, and inflammation and suppressed apoptosis of RA-FLSs by targeting HDAC4. In addition, circ_0008360 positively regulated HDAC4 expression by sponging miR-135b-5p. Circ_0008360 inhibited the proliferation, migration, and inflammation and facilitated apoptosis of RA-FLSs by sponging miR-135b-5p and upregulating HDAC4, providing a potential target for prevention and treatment of RA. [ABSTRACT FROM AUTHOR]

Inflammatory responses after intracerebral hemorrhage (ICH) contribute to severe secondary brain injury, leading to poor clinical outcomes. However, the responsible genes for effective anti-inflammation treatment in ICH remain poorly elucidated. The differentially expressed genes (DEGs) of human ICH were explored by online GEO2R. Go and KEGG were used to explore the biological function of DEGs. Protein–protein interactions (PPI) were built in the String database. Critical modules of PPI were identified by a molecular complex detection algorithm (MCODE). Cytohubba was used to determine the hub genes. The mRNA-miRNA interaction network was built in the miRWalk database. The rat ICH model was applied to validate the key genes. A total of 776 DEGs were identified in ICH. Go and KEGG analyses indicated that DEGs were mainly involved in neutrophil activation and the TNF signaling pathway. GSEA analysis presented that DEGs were significantly enriched in TNF signaling and inflammatory response. PPI network was constructed in the 48 differentially expressed inflammatory response-related genes. The critical module of the PPI network was constructed by 7 MCODE genes and functioned as the inflammatory response. The top 10 hub genes with the highest degrees were identified in the inflammatory response after ICH. CCL20 was confirmed as a key gene and mainly expressed in neurons in the rat ICH model. The regulatory network between CCL20 and miR-766 was built, and the miR-766 decrease was confirmed in a human ICH dataset. CCL20 is a key biomarker of inflammatory response after intracerebral hemorrhage, providing a potential target for inflammatory intervention in ICH. [ABSTRACT FROM AUTHOR]