Ask about this productRelated genes to: ARID5A Blocking Peptide
- Gene:
- ARID5A NIH gene
- Name:
- AT-rich interaction domain 5A
- Previous symbol:
- -
- Synonyms:
- MRF-1, RP11-363D14
- Chromosome:
- 2q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 2004-01-28
- Date modifiied:
- 2016-10-05
Related products to: ARID5A Blocking Peptide
Related articles to: ARID5A Blocking Peptide
- The microtubule-stabilizing drug paclitaxel remains the standard of care for various solid malignancies but frequently leads to chemotherapy-induced peripheral neuropathy (CIPN). CIPN is a leading cause for premature treatment termination and a significantly reduced quality of life in long-term cancer survivors. The molecular mechanisms of neuro-axonal degeneration, neuroinflammation, and pain in patients treated with paclitaxel remain incompletely understood, and there are currently no predictive biomarkers or preventive treatments. We used human iPSC-derived sensory neurons exposed to paclitaxel to comprehensively model the pathophysiology of CIPN. Neurotoxicity was assessed over time using viability assays and sequential RNA sequencing, as well as deep proteome and lipidomic analyses. We observed a time and dose-dependent decline of cell viability at clinically relevant paclitaxel doses. Sequential RNA sequencing defined JUN as an early immediate gene, followed by the overexpression of genes of the neuronal stress response (e.g., ARID5A, WEE1, DUSP16, GADD45A), neuronal injury and apoptotic pathways (e.g., ATF3, HRK, BBC3 [PUMA], BCL2L11 [BIM], CASP3), neuroinflammation and nociception (CALCB, MMP10, IL31RA, CYSLTR2, C3AR1, TNFRSF12A) and neuronal transduction (e.g., CAMK2A, STOML3, PIRT), while key enzymes of lipid biosynthesis were markedly downregulated (e.g., LSS, HMGCS1, HMGCR, DHCR24). Deep proteome analyses following 48 h of exposure to 100 nM paclitaxel revealed a strong correlation of differentially expressed RNA with proteins, and a marked degradation of essential axonal transport proteins such as kinesins, stathmins, and scaffold proteins. Consistent with the downregulation of rate-limiting enzymes of lipid biosynthesis, lipidome analysis confirmed deregulation of neuronal lipid homeostasis. In summary, paclitaxel induces transcriptomic and proteomic signatures of the neuronal stress response, neuroinflammation, nociception, and disturbed metabolism. These may explain, in part, the clinical phenotype of sensory loss, hypersensitivity, and neuropathic pain frequently observed in patients suffering from CIPN, but constitute pharmacologically addressable targets. - Source: PubMed
Publication date: 2026/02/10
Schinke ChristianMaierhof Smilla KHew LoisFernandez Vallone ValeriaFrahm SilkeTelugu Narasimha SwamyDiecke SebastianIvanov AndranikKovács RichardBeule DieterKirchner MarieluiseMertins PhilippBrüning UlrikeKirwan Jennifer AStachelscheid HaraldEndres MatthiasHuehnchen PetraBoehmerle Wolfgang - Cartilage development and homeostasis require precise regulation by transcriptional and epigenetic networks. PRDM16 is a transcription factor containing zinc finger domains that enable protein-DNA and protein-protein interactions, as well as domains with the capacity for histone methyltransferase activity. However, the detailed molecular mechanisms by which PRDM16 regulates chondrogenesis and chondrocyte identities remain largely unknown. Using our osteochondral lineage-specific, conditional knockout mouse model ( , Prdm16 cKO), we found that loss of Prdm16 in osteochondral lineage cells delays, but does not fully inhibit, endochondral ossification and bone formation in the knee joint. Furthermore, Prdm16 cKO male mice exhibit comparable OA severity between injured and non-injured joints, suggesting that PRDM16 may exert a chondroprotective function. In our hiPSC-derived chondrocyte model, we observed significantly reduced pellet size and DNA content in cells with modulated PRDM16 expression compared to Control, implying a link between PRDM16 and chondrocyte viability. Integrated analysis of single cell RNA-sequencing and CUT&RUN-sequencing revealed that PRDM16 regulates chondrocyte cell fate decisions by altering chromatin accessibility and DNA binding at promoter/enhancer regions of genes essential for chondrogenesis and chondrocyte hypertrophy. Indeed, PRDM16 governs the expression of key chondrogenic regulators including , , , , and hypertrophic driver . Overall, our results provide evidence that PRDM16 serves as an essential genetic and epigenetic regulator of chondrogenesis and chondrocyte phenotype specification in the knee joint through DNA binding and by modulating H3K4me3 histone mark deposition. - Source: PubMed
Publication date: 2026/01/31
Fadial EloiseHansen VictoriaKulzhanova GulzadaTashbib Eliya TazreenaChinta DeekshaKlee AlexisShammas HelenPradhan GourangoWu Chia-Lung - Rheumatoid arthritis (RA) is characterized by joint inflammation and bone erosion. Understanding cytokine pathways, particularly those targeting TNF, is crucial for understanding pathology and advancing treatment development. Arid5a is a noncanonical RNA binding protein (RBP) that augments inflammation through stabilizing proinflammatory mRNAs and enhancing protein translation. We examined published datasets for ARID5A in human RA blood, T cells, and synovial tissues. A stromal cell line, epithelial cells, and primary synovial fibroblasts were used to assess the effect of TNF on Arid5a expression, localization, and function. To determine how TNF induces Arid5a, WT or Traf2-/- stromal cells were treated with NIK or IKK inhibitors. To evaluate the necessity of Arid5a in arthritis progression, Arid5a-/- mice were subjected to collagen-induced arthritis. ARID5A was elevated in patients with RA and reduced by anti-TNF therapy. TNF upregulated Arid5a through the NF-κB1/TRAF2 pathway, causing cytoplasmic relocalization. Arid5a stabilized proinflammatory transcripts and enhanced expression of chemokines that drive RA. Arid5a-/- mice were resistant to collagen-induced arthritis correlating with reduced Th17 cells in synovial tissue. Thus, Arid5a serves as a newly recognized signaling intermediate downstream of TNF that is elevated in human RA and drives pathology in murine CIA, potentially positioning this RBP as a possible therapeutic target. - Source: PubMed
Publication date: 2026/01/23
Li YangDey IpsitaVyas Shachi PSynackova AlzbetaLi DechengLubberts ErikAscherman Dana PDraber PeterGaffen Sarah L - Depression is a psychiatric disorder which affects many aspects of the social life of patients; however, the molecular biological mechanisms underlying its development are not fully understood. Our research reveals that depression onset is associated with BRD2 LLPS-mediated activation of ATG7 super-enhancers (SEs), and we studied BRD2 liquid-liquid phase separation (LLPS) and super-enhancers in depression using chronic mild stress (CMS)-induced rat models and corticosterone-stimulated PC12 cell models. SEs enrichment, core transcription factor ARID5A and target gene ATG7 were found in the prefrontal cortex of depressed rats by ChIP-seq; through in vitro construction of phase separation droplets, fluorescent bleach recovery experiments (FRAP), and verification of the dual luciferase reporter gene, we found that BRD2 mediates transcription through LLPS, driving ATG7 transcriptional activation; while the BET inhibitor JQ1 reverses abnormal ATG7 activation and alleviates depressive behaviors and saving ferritinophagy in animal models of CMS.Our work is the first to elucidate the "phase separation-SEs-ferritinophagy" axis in depression pathogenesis, offering novel therapeutic strategies targeting epigenetic and phase separation mechanisms. It provides new ideas for the pathogenesis and treatment of depression. - Source: PubMed
Publication date: 2025/10/27
Li ZhenWang XiaolingLi QinglianLiu YangpingSi WenwenChen DongfengWang QizhangZhu Meiling - Intranodal palisaded myofibroblastomas with amianthoid fibers (IPM) are rare mesenchymal neoplasms showing a myofibroblastic differentiation. Histopathologically, they might be difficult to distinguish from schwannoma or other neoplasia with spindle cell morphology, especially on limited biopsies. CTNNB1 gene variants have been detected in at least 50% of tumors. In this study, we determined the methylation profile including the copy number variation profile in a series of six patients. These analyses enabled genes with the highest gains or losses compared to myoblasts and fibroblasts to be identified. We identified a new methylation cluster that is not included in the Heidelberg Sarcoma Classifier so far. Furthermore, significantly differentially hypo- and hypermethylated genes compared to normal myoblasts and fibroblasts were detected in all samples, e.g., ARID5A, MIB2, TRIM58, and others were > 17-fold hypomethylated, while NEDD4, RUNX1, SLC8A1, and others were > 75-fold hypermethylated. Additionally, when combining positive ß-catenin expression and sequencing results, the aberrant/mutant CTNNB1 gene was shown in three tumors (75% of analyzed cases) in this IPM series. The present data provides additional support/adjunct to establish the rare diagnosis of intranodal palisaded myofibroblastomas with amianthoid fibers by molecular testing in diagnostically challenging cases. - Source: PubMed
Publication date: 2025/07/18
Leisz SandraScheer MaximilianHildebrandt UweWiegers MerleStrauss ChristianScheller ChristianMentzel Thomasvon Deimling AndreasHarder Anja