Ask about this productRelated genes to: JMJD5 antibody
- Gene:
- KDM8 NIH gene
- Name:
- lysine demethylase 8
- Previous symbol:
- JMJD5
- Synonyms:
- FLJ13798
- Chromosome:
- 16p12.1
- Locus Type:
- gene with protein product
- Date approved:
- 2006-02-17
- Date modifiied:
- 2019-03-19
Related products to: JMJD5 antibody
Related articles to: JMJD5 antibody
- Both KDM8 and c-Myc have been implicated in regulating tumor glucose metabolism. However, whether there is an interaction between KDM8 and c-Myc, and whether KDM8 function is dependent on c-Myc in ovarian cancer (OC) remains unclear. Paired cancerous and paracancerous tissues from five OC patients were analyzed for KDM8 and c-Myc expression using reverse transcription quantitative polymerase chain reaction and Western blot. Co-Immunoprecipitation assays were conducted to verify their potential interaction. Stable OVCAR3 and SKOV3 cell lines overexpressing KDM8 or c-Myc were established. Functional assays (CCK-8, Transwell, colony formation, wound healing, and flow cytometry) were performed to assess proliferation, migration, invasion, colony formation, and apoptosis. Metabolic changes were evaluated by measuring glucose uptake and lactate accumulation using colorimetric and ELISA kits, respectively. Finally, a nude mouse subcutaneous xenograft model was constructed to observe the growth and metabolic levels of OC in vivo. Both mRNA and protein levels of KDM8 and c-Myc were significantly upregulated in ovarian cancer (OC) tissues compared to paracancerous tissues. Furthermore, a direct interaction between KDM8 and c-Myc was identified. Functionally, KDM8 and c-Myc synergistically promoted the malignant behavior of OC cells, including enhanced proliferation, migration, invasion, and colony formation capacities. Additionally, they promoted metabolic reprogramming, as evidenced by increased glucose uptake and lactate accumulation, while concurrently inhibiting apoptosis. However, siRNA-mediated knockdown of c-Myc significantly attenuated these oncogenic effects, reversing the enhanced proliferative, migratory, and metabolic capacities of OC cells. In vivo experiments further verified that the KDM8 /c-Myc axis affects OC growth and metabolic levels. Collectively, our findings indicate that KDM8 and c-Myc cooperate to promote OC progression, which may be mediated through the regulation of glucose metabolism. Notably, KDM8 function is partially dependent on c-Myc in this context. These results provide preliminary evidence supporting KDM8 as a potential candidate target for OC diagnosis and treatment, with further validation required in larger cohorts. - Source: PubMed
Publication date: 2026/04/27
Liu ChunyanXu QianLi ZhuolingYang XiaoliMao BiboGuo LiliLiu XinLiu Wenyuan - KDM8 is a histone demethylase initially characterized for its activity on H3K36me2, although its function is now more widely recognized as a hydroxylase. Through a high-throughput screening on histone demethylases, we identified KDM8 as a regulator of the γH2AX response following ionizing radiation. Experiments using specific reporter substrates revealed that KDM8 depletion increases homologous recombination (HR), while its overexpression reduces HR. This shift is counterbalanced by a concomitant decrease in non-homologous end joining (NHEJ), an effect partly independent of its demethylase activity and unrelated to cell cycle alterations. Despite this imbalance, cellular sensitivity to DNA-damaging agents - such as ionizing radiation, mitomycin C, and camptothecin - remains unchanged. FRET experiments in living cells demonstrated an interaction between KDM8 and Rad51 after DNA damage induced by camptothecin. These findings identify KDM8 as a key player in DSB repair, specifically influencing HR. - Source: PubMed
Publication date: 2026/04/19
Fages JérémieBergoglio ValérieJulia EmmanuelCintori LuanaChailleux CatherineFourez Anne-LisePonsolle NatachaTrouche DidierCanitrot Yvan - Hypertrophic cardiomyopathy (HCM) is a prevalent cardiovascular disorder affecting populations worldwide, characterized by abnormal thickening of the heart muscle.(Supporting S1) The development of HCM is influenced by multiple factors, including genetic mutations, geographical conditions, lifestyle, and environmental exposures. The availability of extensive genomic datasets in public repositories provides an opportunity to identify potential genetic contributors and functional biomarkers associated with HCM. Previous studies have highlighted the pivotal role of the MYBPC3 gene in the pathogenesis of HCM. In this study, computational analyses were performed to predict gene mutations and functional biomarkers using RNA-sequencing and whole exome sequencing datasets. A total of 12 RNA-sequencing samples, comprising four healthy controls and eight HCM cases, along with 12 exome sequencing datasets, were retrieved from the Gene Expression Omnibus (GEO) database. RNA-sequencing analysis identified the top 20 differentially expressed genes associated with HCM, including MIB2, ZBTB48, MYBPC3, PRPF40B, CD27-AS1, MYH7, WDR90, KDM8, BCAM, ZSWIM9, KANK3, CCDC85A, ZNF512B, POLR3H, NUP210, PSMG4, GPLD1, GNL1, SH2D3C, and COL4A6. Among these, MYH7 exhibited the highest expression level, showing strong similarity to MYBPC3 in its association with HCM. Whole exome sequencing analysis further identified a panel of variant genes including MYBPC3, MYH6, MYH7, TNT, Titin, Desmin, ACE1, TGF-beta, Ang-2, SGCG, SGCA, DMD, and LaminA/C, all previously implicated in HCM pathophysiology. This integrative study underscores the correlation between differential gene expression patterns and clinical variants in HCM, providing valuable insights into the molecular mechanisms underlying the disease. - Source: PubMed
Publication date: 2025/11/21
Cn PrashanthaR RamachandraNm GuruprasadReddy Vaddi Damodara - In most solid tumors, hypoxia is a critical physical attribute that reprograms malignant cells into a highly metastatic state. Specifically, hypoxia is a well-established inducer of cellular plasticity, which is associated with treatment resistance and metastasis. Furthermore, hypoxia exacerbates chromosomal instability (CIN), a hallmark of cancer that can be initiated by the loss of and a key contributor to metastasis. Despite this, the mechanisms by which malignant cells concurrently co-opt these elements of hypoxic adaptation to promote metastasis remains unknown. Here we report that hypoxia promotes metastasis by suppressing the JmjC-containing histone lysine demethylase Kdm8. CRISPR/Cas9-mediated targeting of in a ;-driven mouse model of pancreatic ductal adenocarcinoma robustly rewires the malignant cell transcriptomic programs, leading to a profound loss of the epithelial morphology and widespread metastatic disease. Mechanistically, suppression in normoxia recapitulates major aspects of the global epigenetic changes and the transcriptomic rewiring induced by hypoxia. Moreover, deficiency leads to mitotic defects, increased micronuclei formation, copy number gains, and enhanced CIN. Of note, disruption of Kdm8's demethylase function phenocopies the effects of loss, whereas expression of hypermorphic Kdm8 variants that are resistant to hypoxic suppression reduces metastasis beyond the levels achieved by the wildtype counterpart. Through the suppression of Kdm8 demethylase activity, hypoxia unleashes a potent metastatic program by simultaneously advancing cellular plasticity and CIN. - Source: PubMed
Publication date: 2025/10/01
Gunasekaran Pradeep MoonWang QianqianChang Yoke-ChenGuseva PolinaChauhan RajikaKley AlexanderLee GeneRoy Siddharth GhoshMasoudpoor YousefRoberts ArthurWalton Kelly WatkinsFranciosa LucyannBhat ShafiqZachariah EmmanuelPatel KishanZhou ZhongrenChen WenjinNi Julie ZhouliGu Sam GuopingMontagna CristinaChiou Shin-Heng - In most solid tumors, hypoxia constitutes a defining microenvironmental feature that reprograms malignant cells into a highly metastatic state by driving cellular plasticity and exacerbating chromosomal instability (CIN). However, the mechanisms by which cancer cells concurrently co-opt these elements of hypoxic adaptation to promote metastasis remains poorly understood. Here, we report that hypoxia promotes metastasis by suppressing the JmjC-containing histone lysine demethylase Kdm8. CRISPR/Cas9-mediated targeting of in a ;-driven mouse model of pancreatic ductal adenocarcinoma (PDA) robustly rewires the malignant cell transcriptomic programs, leading to a profound loss of the epithelial morphology and widespread metastatic disease. In PDA patients, a high KDM8-induced gene signature is associated with reduced metastatic burden and better survival in advanced disease. Notably, suppression in normoxia recapitulates key aspects of the global epigenetic and transcriptomic rewiring, mitotic spindle defects, and CIN induced by hypoxia. Moreover, disruption of Kdm8's demethylase activity phenocopies loss, whereas expression of hypermorphic Kdm8 variants resistant to hypoxic suppression markedly reduces metastasis beyond the levels achieved by the wildtype protein. Through the suppression of Kdm8 demethylase function, hypoxia unleashes a potent metastatic program by simultaneously advancing cellular plasticity and CIN. - Source: PubMed
Publication date: 2025/08/29
Gunasekaran Pradeep MoonWang QianqianChang Yoke-ChenGuseva PolinaChauhan RajikaKley AlexanderLee GeneRoy Siddharth GhoshMasoudpoor YousefRoberts ArthurWalton Kelly WatkinsFranciosa LucyannBhat ShafiqZachariah EmmanuelPatel KishanZhou ZhongrenChen WenjinNi Julie ZhouliGu Sam GuopingMontagna CristinaChiou Shin-Heng