Ask about this productRelated genes to: PKNOX2 antibody
- Gene:
- PKNOX2 NIH gene
- Name:
- PBX/knotted 1 homeobox 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 11q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-10-01
- Date modifiied:
- 2015-09-04
Related products to: PKNOX2 antibody
Related articles to: PKNOX2 antibody
- This study aimed to elucidate the molecular mechanism by which FBXW4 suppresses the progression of lung adenocarcinoma (LUAD). Functional experiments demonstrated that FBXW4 significantly inhibited LUAD cell proliferation, migration, and invasion, while promoting apoptosis. Furthermore, rescue experiments indicated that PKNOX2 silencing partially reversed the tumor-suppressive effects of FBXW4. Mechanistically, FBXW4 facilitated the ubiquitination and degradation of DNMT1, leading to a decrease of methylation of the promoter. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays confirmed that transcriptionally activated by directly binding to its promoter. In addition, FHL1 was identified as a functional downstream effector responsible for mediating the inhibitory role of PKNOX2 in LUAD malignancy. These findings reveal a previously uncharacterized FBXW4/DNMT1/PKNOX2/FHL1 regulatory axis, providing mechanistic insight into LUAD suppression and potential therapeutic strategies. - Source: PubMed
Publication date: 2025/12/20
Qu BinRen YuxiShen HaomingSun Lisha - African indigenous cattle harbor rich genetic diversity shaped by long-term adaptation to tropical climates and endemic diseases, notably trypanosomiasis. To investigate the genetic basis of natural disease resistance, we analyzed 33,147 SNPs in 1,047 individuals from 17 breeds using complementary selection scans (iHS, XP-EHH, and Rsb) in a multi-cohort framework. Fifteen pairwise comparisons across six breed groups enabled robust detection of recent positive selection, capturing both within-breed and breed-specific adaptive signals. We identified 229 selective regions, with 47 outlier SNPs consistently detected by multiple methods. Selection signals were enriched on chromosomes 5, 7, and 29, containing candidate genes such as ATF4, PKNOX2, DNAJB7, TEF, NFE2, and several SPINK and HOXC family members, many associated with immune function and trypanosome challenge response. These genomic regions represent promising targets for the development of breeding strategies aimed at enhancing disease resilience. By identifying genomic regions under selection, this study provides interesting insights for sustainable livestock improvement and conservation efforts in West and Central Africa. Our findings support the integration of indigenous genetic resources into breeding programs designed to optimize productivity while maintaining resilience to environmental and disease pressures. - Source: PubMed
Publication date: 2025/12/01
Bitew Mulusew KassaPaguem ArchileAbanda BabetteAchukwi Daniel MbunkaManchang Kingsley TanyiPreuß SiegfriedHanotte OlivierSenczuk GabrieleRenz AlfonsEisenbarth AlbertPilla Fabio - Much effort has been made to uncover the cellular heterogeneities of human hearts by single-nucleus RNA sequencing. However, the cardiac transcriptional regulation networks have not been systematically described because of the limitations in detecting transcription factors. In this study, we optimized a pipeline for isolating nuclei and conducting single-nucleus RNA sequencing targeted to detect a higher number of cell signal genes and an optimal number of transcription factors. With this unbiased protocol, we characterized the cellular composition of healthy human hearts and investigated the transcriptional regulation networks involved in determining the cellular identities and functions of the main cardiac cell subtypes. Particularly in fibroblasts, a novel regulator, PKNOX2, was identified as being associated with physiological fibroblast activation in healthy hearts. To validate the roles of these transcription factors in maintaining homeostasis, we used single-nucleus RNA-sequencing analysis of transplanted failing hearts focusing on fibroblast remodelling. The trajectory analysis suggested that PKNOX2 was abnormally decreased from fibroblast activation to pathological myofibroblast formation. Both gain- and loss-of-function in vitro experiments demonstrated the inhibitory role of PKNOX2 in pathological fibrosis remodelling. Moreover, fibroblast-specific overexpression and knockout of PKNOX2 in a heart failure mouse model induced by transverse aortic constriction surgery significantly improved and aggravated myocardial fibrosis, respectively. In summary, this study established a high-quality pipeline for single-nucleus RNA-sequencing analysis of heart muscle. With this optimized protocol, we described the transcriptional regulation networks of the main cardiac cell subtypes and identified PKNOX2 as a novel regulator in suppressing fibrosis and a potential therapeutic target for future translational studies. - Source: PubMed
Publication date: 2024/04/22
Chen LiangLi HaotongLiu XiaoruiZhang NingningWang KuiShi AntengGao HangAkdis DenizSaguner Ardan MXu XinjieOsto ElenaVan de Veen WillemLi GuangyuBayés-Genís AntoniDuru FiratSong JiangpingLi XiangjieHu Shengshou - This study aimed to explore the pharmacogenetic variability associated with the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy Chinese subjects. - Source: PubMed
Publication date: 2024/03/28
Liu ZhiyanXie QiufenZhao XiaTan YunlongWang WenpingCao YuWei XiaohuaMu GuangyanZhang HanxuZhou ShuangWang XiaobinCao YingLi XinChen SongCao DuanwenCui YiminXiang Qian - Low cardiorespiratory fitness, measured as maximal oxygen uptake (V̇o), is associated with all-cause mortality and disease-specific morbidity and mortality and is estimated to have a large genetic component (∼60%). However, the underlying mechanisms explaining the associations are not known, and no association study has assessed shared genetics between directly measured V̇o and disease. We believe that identifying the mechanisms explaining how low V̇o is related to increased disease risk can contribute to prevention and therapy. We used a phenome-wide association study approach to test for shared genetics. A total of 64,479 participants from the Trøndelag Health Study (HUNT) were included. Genetic variants previously linked to V̇o were tested for association with diseases related to the cardiovascular system, diabetes, dementia, mental disorders, and cancer as well as clinical measurements and biomarkers from HUNT. In the total population, three single-nucleotide polymorphisms (SNPs) in and near the follicle-stimulating hormone receptor gene () were found to be associated (false discovery rate < 0.05) with serum creatinine levels and one intronic SNP in the Rap-associating DIL domain gene () with diabetes type 1 with neurological manifestations. In males, four intronic SNPs in the PBX/knotted homeobox 2 gene () were found to be associated with endocarditis. None of the association tests in the female population reached overall statistical significance; the associations with the lowest values included other cardiac conduction disorders, subdural hemorrhage, and myocarditis. The results might suggest shared genetics between V̇o and disease. However, further effort should be put into investigating the potential shared genetics between inborn V̇o and disease in larger cohorts to increase statistical power. To our knowledge, this is the first genetic association study exploring how genes linked to cardiorespiratory fitness (CRF) relate to disease risk. By investigating shared genetics, we found indications that genetic variants linked to directly measured CRF also affect the level of blood creatinine, risk of diabetes, and endocarditis. Less certain findings showed that genetic variants of high CRF might cause lower body mass index, healthier HDL cholesterol, and lower resting heart rate. - Source: PubMed
Publication date: 2023/08/14
Nordeidet Ada NKlevjer MarieWisløff UlrikLangaas MetteBye Anja