Ask about this productRelated genes to: KLHL4 Blocking Peptide
- Gene:
- KLHL4 NIH gene
- Name:
- kelch like family member 4
- Previous symbol:
- -
- Synonyms:
- KIAA1687, DKELCHL, KHL4
- Chromosome:
- Xq21.31
- Locus Type:
- gene with protein product
- Date approved:
- 2000-05-02
- Date modifiied:
- 2016-11-15
Related products to: KLHL4 Blocking Peptide
Related articles to: KLHL4 Blocking Peptide
- Oral squamous cell carcinoma (OSCC) is the most prevalent form of head and neck squamous cell carcinoma (HNSCC), characterized by high incidence rates, frequent recurrence and metastasis, and low survival rates. KLHL4, a member of the Kelch-like family proteins, plays a significant role in cancer. However, the role of KLHL4 in OSCC remains largely unexplored. In this study, we first identified the aberrant overexpression of KLHL4 in OSCC tissues through Western blotting and immunohistochemistry. Subsequent experiments, including qPCR, colony formation assays, scratch assays, and transwell invasion and migration assays, demonstrated that knockdown of KLHL4 inhibits OSCC growth, migration and invasion in vitro. Furthermore, through the establishment of subcutaneous xenograft models and lung metastasis models in nude mice, we revealed that KLHL4 knockdown suppresses tumor growth and metastasis in vivo. We also found that KLHL4 knockout inhibited 4NQO-induced OSCC progression. Mechanistically, co-immunoprecipitation confirmed the physical interaction between KLHL4 and EGFR, while rescue experiments using EGF and Afatinib demonstrated the functional dependency of KLHL4 on EGFR pathway activation. Clinical analysis of a 112-case OSCC tissue microarray revealed that high KLHL4 expression correlated significantly with lymph node metastasis and predicted poor patient overall survival, which was independently validated in a public HNSCC cohort. Overall, our research highlights the critical role of KLHL4 in the malignant progression of OSCC through upregulating the EGFR signaling pathway, indicating its potential as a therapeutic target for OSCC treatment. - Source: PubMed
Publication date: 2025/12/26
Zhang YingxinRen YuanWang YimeiLiu MingCheng FangbuLi HaiyunSun SiluZhou XikunYang JiantangLi Jing - Ferroptosis constitutes a pivotal pathological event following spinal cord injury and presents substantial challenges to the restoration of neurological function. Cystine-glutamate transporter SLC7A11 is essential for maintaining cellular redox homeostasis and resisting ferroptosis. However, the mechanisms underlying neuronal ferroptosis caused by SLC7A11 downregulation following spinal cord injury remain unclear. Herein, we provide evidence that tumor protein 53, a negative regulator of SLC7A11, was significantly upregulated post-spinal cord injury. Transcriptomic analysis indicated that tumor protein 53 was associated with injury severity. We subsequently confirmed that tumor protein 53 inhibition restored the expressions of SLC7A11 and glutathione peroxidase 4, alleviated neuronal ferroptosis, and improved neurological function in a contusion spinal cord injury rat model. The regulatory effects of tumor protein 53 on the transcription and ubiquitination of SLC7A11 were further elucidated using chromatin immunoprecipitation polymerase chain reaction and cleavage under targets and tagmentation techniques. Additionally, Kelch-like protein 4, an E3 ubiquitin ligase adaptor, was demonstrated to play an important role in the tumor protein 53-mediated ubiquitination of SLC7A11. In summary, the present study elucidated the possible mechanisms of tumor protein 53-mediated neuronal ferroptosis in spinal cord injury, thereby providing potential targets and insights for clinical translation. - Source: PubMed
Publication date: 2025/09/03
Kang YuLi QiangweiZhao TianlunZhang HaojieSun YuejianZhang YilongAn DaYin ZongshengXuan YongXie Peigen - Gastric cancer, a prevalent and fatal form of cancer worldwide, is manifested at different age ranges during the lifespan. Approximately one‑third of newly diagnosed gastric cancer cases are early‑onset gastric cancer (EO‑GC), which affects individuals under the age of 50 years. EO‑GC tends to be more aggressive than late‑onset gastric cancer (L‑GC), with a faster and multifocal disease progression. Furthermore, EO‑GC is associated with early metastatic disease. Recent research has underscored the need for a deeper understanding of EO‑GC that promotes therapeutic approaches specific to EO‑GC. The present study determined the main transcriptomic differences between EO‑GC and L‑GC. Transcriptomic expression data from The Cancer Genome Atlas‑Stomach Adenocarcinoma were explored to elucidate whether age is associated with a specific genomic expression pattern and is associated with gastric cancer. Subsequently, a differential gene expression analysis of the EO‑GC vs. L‑GC groups was performed, providing new insights into EO‑GC gene expression characteristics and their association with survival outcomes. Furthermore, the study focused on whether the influence of representative gene expression in EO‑GC cases ( and genes) may be associated with its aggressive phenotype and methylation profiles of these patients. In this review, the necessity of incorporating age as a crucial element in understanding the disparities in outcomes for EO‑GC cases in public datasets was discussed. Furthermore, this insight may be useful for targeted early personalized clinical interventions to improve patient prognosis and survival rates in EO‑GC cases. - Source: PubMed
Publication date: 2025/06/20
Gómez-Valenzuela FernánSilva IanRetamal Ignacio NGarcía-Bloj BenjamínDe Mayo Glasser TomásMuñoz-Medel MatíasGómez AlexSan Martín CristopherSánchez CarolinaPinto FelipeAravena PaolaSabioncello Andrea CGarrido Villanueva MarceloSigler Chávez FernandoCorvalán IgnacioBarrios HenryErpel José MManque Patricio AGodoy Juan AGarrido Marcelo - Molecular mechanisms regulating vascular development and hematopoiesis are still incompletely understood. The KLHL (Kelch-like) family of proteins function as adapters to target proteins for ubiquitination. However, their role in vascular development has not been previously analyzed. Here we have characterized a novel regulator of vascular development, kelch-like family member 4 (klhl4) in zebrafish. We show that zebrafish klhl4 is expressed in early vascular endothelial and hematopoietic progenitors, while its expression is restricted to vascular endothelial cells during later developmental stages. To determine the functional role of klhl4, we generated loss-of-function zebrafish mutants using CRISPR/Cas9 genome editing. klhl4 mutant embryos were viable, yet they exhibited delayed sprouting of intersegmental vessels (ISVs), which correlated with reduced expression of vascular endothelial and erythroid specific molecular markers. Time-lapse imaging showed that vascular endothelial and hematopoietic progenitor cells exhibit delayed migration towards the midline and undergo increased apoptosis and reduced proliferation in klhl4 mutants. Expression of npas4l and etv2/etsrp, two master regulators of endothelial and hematopoietic development, was reduced in klhl4 mutants, suggesting that some vascular defects could be caused by the reduction of npas4l and etv2 expression. However, npas4l or etv2 overexpression failed to rescue ISV sprouting defects in klhl4 mutants, suggesting that klhl4 may promote vasculogenesis by additional mechanisms. In summary, our findings demonstrate a novel role for zebrafish klhl4 in regulating vascular endothelial and hematopoietic development during embryogenesis. Because the Klhl4 protein sequence is highly conserved between different vertebrates, it is likely that it may play a similar role in other organisms. - Source: PubMed
Publication date: 2025/05/20
Ferrari KaitlinGurung SumanLoges Luiza NBatta Surya Prakash RaoHammond Myles AGriciunaite MartynaDeMoya RicardoRestrepo Nicole KSumanas Saulius - The incidence of thyroid papillary carcinoma (PTC) is increasing annually, causing both physical and psychological pressure on patients. Therefore, early recognition and specific interventions for PTC are crucial. The objective of this study is to explore novel diagnostic marker and precise intervention targets for PTC. - Source: PubMed
Publication date: 2025/03/17
Zhang JingshuSun Ping