Ask about this productRelated genes to: MARK3 antibody
- Gene:
- MARK3 NIH gene
- Name:
- microtubule affinity regulating kinase 3
- Previous symbol:
- -
- Synonyms:
- CTAK1, KP78, PAR-1A
- Chromosome:
- 14q32.32-q32.33
- Locus Type:
- gene with protein product
- Date approved:
- 1997-10-27
- Date modifiied:
- 2018-02-13
Related products to: MARK3 antibody
Related articles to: MARK3 antibody
- Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat due to the absence of effective targeted therapies. In this study, we demonstrate that elevated expression of microtubule affinity-regulating kinase 2 (MARK2), but not other MARK family members (MARK1, MARK3, and MARK4), correlates with poor prognosis in TNBC patients. Silencing MARK2 impairs TNBC progression via inhibition of mutant p53 (mutp53) signaling. In contrast, silencing any of the other three MARKs either enhances or does not affect TNBC cell growth or migration and has no impact on mutp53 expression. Notably, direct knockdown of mutp53 recapitulates the effects of MARK2 ablation in TNBC cells, further supporting a functional linkage. Moreover, ectopic expression of either wild-type (WT) MARK2 or its kinase-dead (KD) mutant enhances mutp53 signaling and promotes TNBC progression; however, MARK2 overexpression does not alter wild-type p53 (wtp53) expression or cell growth in luminal breast cancer cells. Significant inverse correlations are also observed between the expression levels of MARK2, THBS1, or HBEGF (two direct target genes of mutp53) and both overall and disease-free survival in TNBC patients harboring mutTP53, whereas no such association exists between MARK2 and survival in breast cancer subtypes expressing wtTP53. MARK2 is predominantly localized in the nucleus of TNBC cells, where it interacts with and stabilizes mutp53 through its UBA and Spacer domains. Consistent with this, MARK2-ΔUBA or MARK2-ΔSpacer mutant proteins fail to bind mutp53 or sustain its signaling, thereby acting as dominant-negative inhibitors that suppress TNBC progression. Collectively, our findings indicate that suppressing MARK2 expression, rather than inhibiting its kinase activity, may represent an effective therapeutic strategy for TNBC with mutTP53. - Source: PubMed
Zhang MinZhu XilongCui MengqianGuan YinanZhang YongWeiss Stephen JChen JunYao YongzhongFu RongWu Zhaoqiu - The aim of this study was to find potential drug targets of knee osteoarthritis (KOA) through druggable genome and Mendelian randomization (MR) analysis. Through integrating data from expression quantitative trait loci at different tissue and cellular levels, we identified potential therapeutic targets for KOA using drug target MR and single-cell MR analyses. Based on peripheral protein quantitative trait locus (pQTL) data, we validated the identified targets at the proteomic level using summary data-based MR and Heterogeneity in Dependent Instrument tests. Meanwhile, we used mediation MR analysis to explore possible mechanisms of action of the identified targets in KOA. To capture tissue specificity, we further applied the genetically informed spatial mapping (gsMap) framework, integrating KOA genome-wide association studies with spatial transcriptomics of E16.5 mouse embryonic tissues. We identified 12 and 5 potential therapeutic targets for KOA from peripheral and central tissues, respectively. Mitogen-activated protein kinase (MAPK3) and MARK3 were validated at the proteomic level, with MAPK3 showing a genetic association with reduced risk against KOA in both peripheral and central tissues. Single-cell MR analysis revealed that Lymphocyte antigen 6 D (LY6D) was associated with an increased risk of KOA in exogenous cells, MAPK3 showed a protective association in inhibitory neuron cells, and transforming growth factor alpha (TGFA) was associated with a reduced risk of KOA in oligodendrocyte precursor cells. Mediation MR analysis showed that body mass index (BMI) played a 16.6% mediating role in the causal association between MAPK3 and KOA. GsMap analysis revealed significant enrichment of KOA signals in cartilage primordium, cartilage, lung, and brain tissues. Finally, we proposed 16 potential therapeutic targets for KOA from both central and peripheral perspectives. Meanwhile, we found that BMI served as a mediator to mediate the causal effect between MAPK3 and KOA. Further experiments are needed in the future to verify the mechanism of action of the targets identified in this study in KOA. - Source: PubMed
Publication date: 2025/12/16
Sun ChiyunLiu RuikangFan WeimingHu JiamingSun ChuanruiTang KaiqiangShan PengchengZhang Hongmei - To validate the Hearing Utility Measure (HUM), a tool designed to quantify hearing loss impact on health and quality of life for use in economic evaluation. - Source: PubMed
Publication date: 2025/10/13
Dixon Peter RShah Anuja HMcRackan Theodore RFeeny DavidCushing Sharon LTomlinson GeorgeChen Joseph M - Crohn disease (CD) is an immune-mediated chronic inflammatory disease of the gastrointestinal tract. In addition to common intestinal symptoms such as abdominal pain and diarrhea, it may be combined with extraintestinal manifestations in the joints, skin, and biliopancreatic tract. Previous studies have reported a causal association between inflammatory bowel disease and acute pancreatitis (AP), but the underlying pathogenesis remains unclear. It is clinically important to investigate the genetic co-morbidity between CD and AP for the diagnosis and management of extraintestinal manifestations. Bibliometric analysis was utilized to explore the CD-AP relationship. A two-sample Mendelian Randomization (MR) approach assessed the causality. Clinical data from 23 patients with a documented history of CD at 3 major gastroenterology centers were examined. Expression quantitative trait loci data including 5421 cis-expression quantitative trait loci genes from blood samples of 31,684 individuals across 37 cohorts identified variant-associated genes. Transmembrane protein 258 (TMEM258) was further investigated through bulk and single-cell RNA sequencing. Its expression was quantified via RT-PCR in intestinal samples from a dextran sulfate sodium-induced acute colitis mouse model. Immune cell infiltration analysis was performed to evaluate the immune correlations. Mediators between CD and AP were identified from 731 candidate immune cells by two-step MR and mediation analysis. Persistent literature reports have noted associations between inflammatory bowel disease and AP. Our two-sample MR analysis revealed a potential causal relationship between CD and AP (odds ratio = 1.043; 95% CI: 1.011-1.075; P = .008). In 23 patients with CD and AP co-morbidity, late-onset AP predominantly occurs in CD patients with the L1B2 phenotype compared to early-onset AP. DHX58, KLRG1, MARK3, and TMEM258 were causal biomarkers in both conditions. TMEM258 mediates the immune response in this comorbidity and is highly expressed in mesenchymal cells within the inflamed intestinal tissues of CD patients. TMEM258 expression positively correlated to M1 macrophages and plasma cells, and negatively correlated to neutrophils and naïve CD8+ T cells. CD28+ double negative T cells and naïve CD8+ T cells mediate the predictive effect of CD on the onset of AP. Through MR and multi-omics analyses, our study demonstrates that TMEM258 is a shared susceptibility gene for CD and AP, increasing the risk of AP in CD by reducing T cell infiltration. - Source: PubMed
Lu GuijunZhou ShengyiShen JiaxinChi XintongWang YupingZhang XinyiWei XujinLiu Wenming - clinical trials that simulate individualized mechanisms of action offer a powerful approach to assess drug efficacy across large and diverse patient populations, while also enabling the identification of predictive biomarkers. In this study, we conducted an clinical trial of first-line, single-agent regorafenib in 399 elderly patients with metastatic colorectal cancer (mCRC). Individualized network-based models were constructed using patient-specific differential transcriptomic profiles and employed to simulate the target-specific effects of regorafenib. From this analysis, we identified both predictive and mechanistic biomarkers of treatment response. Notably, four proteins-MARK3, RBCK1, LHCGR, and HSF1-emerged as dual biomarkers, showing associations with both response mechanisms and predictive potential. Three of these (MARK3, RBCK1, and HSF1) were validated in an independent cohort of mCRC patients and were also found to be targets of previously reported regorafenib-predictive miRNAs. This study demonstrates a novel systems biology strategy for evaluating drug response , leveraging transcriptomic data to simulate individual treatment outcomes and uncover clinically relevant biomarkers. Our findings suggest that such approaches may serve as valuable complements to traditional clinical trials for assessing drug efficacy and guiding precision oncology. - Source: PubMed
Publication date: 2025/09/15
García-Illarramendi Juan ManuelMatos-Filipe PedroMas Jose ManuelFarrés JudithDaura Xavier