MiR‐1193 represses the proliferation and induces the apoptosis of interleukin‐1β‐treated fibroblast‐like synoviocytes via targeting JAK3

Abstract

Objectives: To explore the roles of miR-1193/Janus kinase 3 (JAK3) axis and the potential mechanism in rheumatoid arthritis (RA). Methods: The dysregulated genes and microRNAs (miRNAs) were screened using the datasets of GSE12021 and GSE72564, while the upstream miRNA of JAK3 was forecasted by TargetScan. Then the MH7A cells were treated with interleukin-1β (IL-1β) to induce local inflammation. Double luciferase report assay was used to estimate the association between JAK3 and miR-1193. Flow cytometry and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays were taken to analyze the apoptosis and proliferation of MH7A cells with IL-1β-induced inflammation, respectively. The relative expression of genes and proteins were detected by quantitative real-time polymerase chain reaction and western blot analyses. Finally, rescue experiments were employed to explore the effects of miR-1193/JAK3 axis on IL-1βinduced inflammation. Results: JAK3 was notably up-regulated in RA, and was targeted and negatively regulated by miR-1193 which was lowly expressed in RA tissues and IL-1β-treated cells. MiR-1193 mimic significantly inhibited while miR-1193 inhibitor promoted the proliferation of MH7A cells with IL-1β-induced inflammation. Furthermore, overexpression of JAK3 presented auxo-action while depletion of JAK3 exhibited inhibitory effect on the proliferation of MH7A cells with IL-1β-induced inflammation, which could be weakened by miR-1193 mimic and miR-1193 inhibitor, respectively. Analogously, JAK3 recovered the cell proliferation that inhibited by miR-1193 mimic and inhibited cell apoptosis enhanced by miR-1193 mimic. Conclusion: Up-regulation of miR-1193 suppressed the proliferation and expedited the apoptosis of MH7A cells with IL-1β-induced inflammation through targeting JAK3, which might provide novel understanding on the mechanism underlying RA.

Circulating microRNAs Suggest Networks Associated with Biological Functions in Aggressive Refractory Type 2 Celiac Disease

“…Notably, miR-181b is strongly associated with inflammation, but only a little information has been reported in the literature on the specific miR-181b-2-3p, which seems more appropriately linked to drug response/resistance than to doxorubicin in cancer [ 61 , 62 ]. miR-1193 inhibits fibroblast proliferation, is associated with the apoptosis of fibroblasts exposed to interleukin-1β in a rheumatoid arthritis model [ 63 ], and plays a role as an oncosuppressor in human T-cell leukemia cells [ 64 ]; monitoring changes in their levels could be relevant as it may possibly be related to the appearance of malignant pathologies. In contrast, functionally miR-770-5p and miR-1226-3p promote tumorigenicity in several types of cancers [ 65 , 66 ].…”

Epigenetic Regulation of Immune and Inflammatory Responses in Rheumatoid Arthritis

“…The original article of GSE72564 just selects a suitable miRNA for downstream research. The function of all miRNAs has not been analyzed ( 27 ). While GSE89408 mainly analyzed the functions of differentially expressed genes related to RA ( 28 ).…”

Identification of Tissue-Specific Expressed Hub Genes and Potential Drugs in Rheumatoid Arthritis Using Bioinformatics Analysis

“…Del Rey et al conducted transcriptional analysis of normal and pathological synoviocytes using microarray expression profiling (Del Rey et al, 2012). Georgel P et al used high throughput expression analysis to evaluate the overall miRNA expression level in fibroblastlike synoviocytes (FLS) isolated from RA patients in comparison with FLS from osteoarthritic (OA) patients (Liu and Ren, 2020). Bi et al assessed the differential expression profiles of lncRNA in FLSs between the RA group and the healthy control groups (Bi et al, 2019).…”