Background: Gouty arthritis is the most frequently diagnosed inflammatory arthritis worldwide. Dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, contributes to various inflammatory disorders via activating NLRP3 inflammasome. However, the biological role of Drp1 in gouty arthritis remains undefined. Methods: A mouse model of monosodium urate (MSU)-induced gouty arthritis and MSU-stimulated macrophages were established as in vivo and in vitro models, respectively. Histological changes were assessed by H&E and IHC analysis. RT-qPCR and western blot were used to detect the expression of Drp1 and the key molecules in joint tissues and macrophages. Cytokine secretion was measured by ELISA assay, and antioxidant enzymes activities and LDH release were monitored using commercial kits. Mitochondrial structure and functions were assessed by transmission electron microscopy (TEM) and MitoSOX staining. Co-IP and GST pull-down assay were used to detect the direct interaction between USP16 and Drp1, as well as the ubiquitination of Drp1. Results: Drp1 was elevated in MSU-induced gouty arthritis model, and it induced gouty arthritis via NF-κB pathway and NLRP3 inflammasome activation. In addition, Drp1 activated NF-κB/NLRP3 signaling via modulating mitochondrial fission. Mechanistically, USP16 mediated deubiquitination and stabilization of Drp1 through its direct interaction with Drp1. Functional studies further showed that USP16 was highly expressed in MSU-stimulated macrophages and induced gouty arthritis via Drp1-dependent NLRP3 inflammasome activation. Conclusion: Deubiquitinase USP16 induced gouty arthritis via Drp1-dependent mitochondrial fission and NF-κB/NLRP3 signaling.

Non‑coding RNAs serve essential roles in regulating mRNA and protein expression and dysregulation of non‑coding RNAs participates in a variety of types of cancer. microRNAs (miRNAs/miRs), which are 21‑24 nucleotides non‑coding RNAs, have been shown to be important for the development of gastric cancer (GC). However, the role of miR‑486‑5p in GC remains to be elucidated. The present study found that miR‑486‑5p was downregulated in GC tissues. Comparing with gastric normal cells GES‑1, GC cells, including MKN‑45, AGS, HGC27 and MKN74, had reduced abundance of miR‑486‑5p transcript. CCK8 and colony formation assays demonstrated that GC cell growth and proliferation were enhanced by miR‑486‑5p inhibitors and were suppressed by miR‑486‑5p mimics. miR‑486‑5p also suppressed cell cycle process and migration and promoted apoptosis in GC cells, as verified by propidium iodide (PI) staining, Transwell assay and PI/Annexin V staining. miR‑486‑5p downregulated fibroblast growth factor 9 (FGF9) through combining to its 3'untranslated region. Overexpression of FGF9 accelerated the growth and proliferation of GC cells. The expression of miR‑486‑5p was negatively associated with FGF9 mRNA expression in GC samples. These results revealed that miR‑486‑5p was a tumor suppressor in GC. Downregulation of FGF9 contributed to the role of miR‑486‑5p in GC.

Acidic nuclear phosphoprotein 32 family member E (ANP32E) is a histone chaperone that removes H2A.Z from chromatin. ANP32E is implicated in numerous cellular processes, including cell proliferation, apoptosis and cell differentiation. Increasing evidence suggests that dysregulation of ANP32E expression is strongly associated with carcinogenesis. However, the relationship between ANP32E in the development of gastric cancer (GC) is unknown. The present study aimed to explore the potential role of ANP32E in the development of GC using gain‑of‑function, loss‑of‑function, CCK‑8, colony formation, apoptosis, reverse transcription‑quantitative PCR, immunoblotting and luciferase reporter assay. The results of the present study demonstrated that ANP32E expression levels were significantly increased in GC tissues. ANP32E knockdown markedly inhibited GC cell proliferation and colony formation and significantly induced GC cell apoptosis, whereas overexpression of ANP32E significantly induced GC cell malignancy. Furthermore, the results demonstrated that there was a positive association between ANP32E and NUF2 component of NDC80 kinetochore complex (NUF2) expression levels. By assessing NUF2 expression levels, it was demonstrated that ANP32E promoted tumor cell proliferation and inhibited cell apoptosis by increasing NUF2 expression levels in GC cell lines. In conclusion, the present study indicated that ANP32E may function as an efficient oncogene, which promotes tumorigenesis of GC cells by inducing NUF2 expression.