Trim14-IκBα Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients.

Chronic inflammatory pain is the highest priority for people with osteoarthritis when seeking medical attention. Despite the availability of NSAIDs and glucocorticoids, central sensitization and peripheral sensitization make pain increasingly difficult to control. Previous studies have identified the ubiquitination system as an important role in the chronic inflammatory pain. Our study displayed that the E3 ubiquitin ligase tripartite motif-containing 14 (Trim14) was abnormally elevated in the serum of patients with osteoarthritis and pain, and the degree of pain was positively correlated with the degree of Trim14 elevation. Furthermore, CFA-induced inflammatory pain rat model showed that Trim14 was significantly increased in the L3-5 spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and in turn the inhibitor of nuclear factor Kappa-B isoform α (IκBα) was decreased after Trim14 elevation. After intrathecal injection of Trim14 siRNA to inhibit Trim14 expression, IκBα expression was reversed and increased, and the pain behaviors and anxiety behaviors of rats were significantly relieved. Overall, these findings suggested that Trim14 may contribute to chronic inflammatory pain by degrading IκBα, and that Trim14 may become a novel therapeutic target for chronic inflammatory pain.

m6A-Mediated Upregulation of lncRNA CHASERR Promotes the Progression of Glioma by Modulating the miR-6893-3p/TRIM14 Axis.

Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are dysregulated in glioma. However, the functional roles of lncRNAs in glioma remain largely unknown. In this study, we utilized the TCGA (the Cancer Genome Atlas database) and GEPIA2 (Gene Expression Profiling Interactive Analysis 2) databases and observed the overexpression of lncRNA CHASERR in glioma tissues. We subsequently investigated this phenomenon in glioma cell lines. The effects of lncRNA CHASERR on glioma proliferation, migration, and invasion were analyzed using in vitro and in vivo experiments. Additionally, the regulatory mechanisms among PTEN/p-Akt/mTOR and Wnt/ß-catenin, lncRNA CHASERR, Micro-RNA-6893-3p(miR-6893-3p), and tripartite motif containing14 (TRIM14) were investigated via bioinformatics analyses, quantitative real-time PCR (qRT-PCR), western blot (WB), RNA immunoprecipitation (RIP), dual luciferase reporter assay, fluorescence in situ hybridization (FISH), and RNA sequencing assays. RIP and RT-qRCR were used to analyze the regulatory effect of N6-methyladenosine(m6A) on the aberrantly expressed lncRNA CHASERR. High lncRNA CHASERR expression was observed in glioma tissues and was associated with unfavorable prognosis in glioma patients. Further functional assays showed that lncRNA CHASERR regulates glioma growth and metastasis in vitro and in vivo. Mechanistically, lncRNA CHASERR sponged miR-6893-3p to upregulate TRIM14 expression, thereby facilitating glioma progression. Additionally, the activation of PTEN/p-Akt/mTOR and Wnt/ß-catenin pathways by lncRNA CHASERR, miR-6893-3p, and TRIM14 was found to regulate glioma progression. Moreover, the upregulation of lncRNA CHASERR was observed in response to N6-methyladenosine modification, which was facilitated by METTL3/YTHDF1-mediated RNA transcripts. This study elucidates the m6A/lncRNACHASERR/miR-6893-3p/TRIM14 pathway that contributes to glioma progression and underscores the potential of lncRNA CHASERR as a novel prognostic indicator and therapeutic target for glioma.