Klf4
- Known as:
- Klf4
- Catalog number:
- 059361A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Klf4
Related genes to: Klf4
- Gene:
- KLF4 NIH gene
- Name:
- Kruppel like factor 4
- Previous symbol:
- -
- Synonyms:
- EZF, GKLF
- Chromosome:
- 9q31.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-12-14
- Date modifiied:
- 2016-10-05
Related products to: Klf4
Related articles to: Klf4
- In this study, we investigated the expression patterns, biological functions, and molecular mechanisms of Proline-rich γ-carboxylated Gla protein 1 (PRRG1) in pancreatic cancer pathogenesis. Our bioinformatics analysis revealed that PRRG1 expression is markedly upregulated in human PC tissues compared to normal pancreatic tissues, with elevated levels significantly correlating with poor prognosis and advanced histological grade. We verified the high expression of PRRG1 in pancreatic cancer tissue specimens and pancreatic cancer cell lines. Using established PC cell lines (CFPAC-1 and PATU-8988T), we demonstrated that shRNA-mediated PRRG1 silencing effectively suppressed malignant phenotypes, including cell viability, proliferation, migration, and invasion in vitro. Conversely, lentivirus-induced PRRG1 overexpression enhanced these oncogenic behaviors. RNA-sequencing analysis identified the PI3K-Akt signaling pathway as a key downstream effector of PRRG1, with pathway activation status directly correlating with PRRG1 expression levels. Mechanistically, we identified KLF4 as a critical transcription factor binding to the PRRG1 promoter region. In vivo, PRRG1 knockdown inhibited tumor growth and PI3K-Akt activation in subcutaneous xenograft models, while PRRG1 overexpression accelerated tumor progression. Low-dose warfarin (2uM) decreased the levels of PRRG1 and GAS6/AXL axis, markedly suppressed the pro-tumorigenic effects driven by PRRG1 overexpression in vitro and in vivo. Notably, single-cell sequencing analysis revealing high PRRG1 expression specifically in PC epithelial cells. These PRRG1-positive epithelial cells not only exhibited enriched PI3K-Akt signaling activity but also showed significant interactions with macrophages and endothelial cells, which were further validated in immunocompetent models in vivo. However, warfarin effectively reversed the PRRG1 overexpression-driven changes in TME. In conclusion, our findings establish PRRG1 as a key driver of pancreatic cancer progression through PI3K/Akt pathway activation and KLF4-mediated transcriptional regulation. PRRG1 facilitates the establishment of a pro-tumorigenic and immunosuppressive TME in PC. Low-dose warfarin significantly suppressed the pro-tumorigenic effects and the PRRG1 overexpression-driven alterations in the tumor immune microenvironment. - Source: PubMed
Publication date: 2026/05/10
Chen Jia-JieZhu Xiao-RenGu Qian-HuiLiu Yuan-YuanChen Min-Bin - Plaque regions in atherosclerosis (AS) exhibit sustained moderate hypoxia, which may impair endothelial function and influence vascular smooth muscle cell (VSMC) behavior. This study aims to investigate hypoxia-responsive endothelial-derived long noncoding RNAs (lncRNAs), and their role in enhancing oxidized low-density lipoprotein(ox-LDL)-induced phenotypic switching of VSMCs. - Source: PubMed
Publication date: 2026/05/08
Yin RenqiZhang GuoxinRuan PengQu LefengShen ZhenweiZhi Kangkang - Proliferative vitreoretinal diseases (PVDs) encompass severe ocular disorders such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and epiretinal membranes (ERM), characterized by the formation of fibrovascular membranes that often lead to retinal detachment and vision loss. A central mechanism driving these conditions is the epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, orchestrated by a network of transcription factors (TFs). Among these, zinc finger E-box binding homeobox 1 (ZEB1) emerges as a pivotal regulator by repressing epithelial markers like E-cadherin and inducing mesenchymal markers such as N-cadherin and vimentin, thereby promoting cell migration and fibrotic membrane formation. nuclear factor of activated T cells 5 (NFAT5) contributes to this process by mediating osmotic stress responses and upregulating inflammatory cytokines, which further act upon EMT and fibrosis. activator protein 1 (AP-1) and hypoxia inducible factor 1 subunit alpha (HIF-1α) participate in driving inflammation, extracellular matrix (ECM) remodeling, and angiogenesis. While HIF-1α triggers vascular endothelial growth factor (VEGF) expression under hypoxic conditions, AP-1 modulates matrix metalloproteinases (MMPs) essential for ECM degradation and remodeling. Additional TFs, including Kruppel-like factor 4 (KLF4) and microphthalmia-associated transcription factor (MITF), are vital in maintaining RPE cell identity. Their downregulation under pathological conditions disrupts epithelial integrity and predisposes cells to undergo EMT. Moreover, β-catenin, through its role in the wingless-related integration site (Wnt) signaling pathway, reinforces EMT and ECM remodeling, further enhancing fibrotic progression. Adipocyte enhancer-binding protein 1 (AEBP1) and ZFP36 ring finger protein like 1 (ZFP36L1) also regulate inflammatory responses and ECM dynamics, providing novel post-transcriptional targets for therapeutic intervention. Overall, the synergistic interactions among these TFs create complex feedback loops that amplify pathological changes in PVDs. Targeting these molecular pathways offers promising avenues for developing multi-targeted therapies aimed at saving vision-threatening disease while reducing invasive surgical interventions. - Source: PubMed
Publication date: 2026/05/08
Duveau ClémentRaiss El Harrak YosraDatlibagi AzinePerret JasonWillermain FrançoisDelporte ChristineMotulsky Elie - To investigate the clinicopathological and molecular features of meningioma, and to analyze the characteristic molecular changes in high-grade meningioma (WHO grades 2-3). A total of 139 meningioma specimens from 134 patients treated at Xuanwu Hospital, Capital Medical University from 2015 to 2020 were collected, including 49, 62 and 28 samples of WHO grades 1, 2 and 3 meningiomas, respectively. Clinical data and pathological diagnoses were reviewed. Next-generation sequencing (NGS) was conducted to analyze the associations of molecular biomarkers with clinicopathological features and prognosis. Among the 134 patients, 59 patients (44.0%) were male, and 75 (56.0%) were female, age 57 (49, 66) years old. The most common genetic alteration was NF2 mutation (43.2%, 60/139). In non-NF2 mutated meningiomas, the hotspot genes of detectable mutations were AKT1 (13.7%, 19/139), TRAF7 (9.4%, 13/139), KLF4 (5.7%, 8/139), SMO (5.7%, 8/139), and PIK3CA (1.4%, 2/139). Twelve of the 13 cases TRAF7 alterations co-occurred with other genetic changes. Some molecular alterations were associated with histological subtypes. For instance, NF2 mutations were most frequently detected in psammomatous meningiomas (2/2) and fibrous meningiomas (8/9), while all secretory meningiomas harbored KLF4 mutations (6/6). Some molecular alterations were associated with tumor grade and prognosis. JAK3 mutations (4.3%, 6/139), TERT promoter mutations (3.6%, 5/139), and homozygous deletion of CDKN2A/B (4.3%, 6/139) were exclusively found in high-grade meningiomas. TERT promoter mutations and CDKN2A/B homozygous deletion (versus normal) were both independently associated with poorer prognosis (<0.001 for both). JAK3 mutation was also associated with shorter overall survivals (=0.031). NF2 is the most frequently mutated gene in meningiomas. TERT promoter mutations and CDKN2A/B homozygous deletion occur exclusively in high-grade meningiomas, link to unfavorable prognosis, and can serve as independent diagnostic markers for WHO grade 3 meningioma. JAK3 mutation seems also to be associated with high-grade meningiomas and shorter survivals. - Source: PubMed
Gao MWang L MXiong Y LZhao L HHu Z LZhang X WTeng L H - - Source: PubMed
Publication date: 2026/05/06
Shi YongqiangSong KairongZhou WenmingDong YanboSong WeiRan RuiZhao GuanghaiZhou KaishengNan WeiZhang Haihong