wwox

BACKGROUND: Chronic cigarette smoke exposure decreases lung expression of WWOX which is known to protect the endothelial barrier during infectious models of ARDS. METHODS: Proteomic analysis of WWOX -silenced endothelial cells (ECs) was done using tandem mass tag mass spectrometry (TMT-MS). WWOX -silenced ECs as well as those isolated from endothelial Wwox knockout (EC Wwox KO) mice were subjected to cyclic stretch (18% elongation, 0.5 Hz, 4 hours). Cellular lysates and media supernatant were harvested for assays of cellular signaling, protein expression, and cytokine release...

We reported that a 31-amino-acid Zfra protein (zinc finger-like protein that regulates apoptosis) blocks neurodegeneration and cancer growth. Zfra binds WW domain-containing oxidoreductase (WWOX) to both N - and C -termini, which leads to accelerated WWOX degradation. WWOX limits the progression of neurodegeneration such as Alzheimer's disease (AD) by binding tau and tau-hyperphosphorylating enzymes. Similarly, Zfra binds many protein targets and accelerates their degradation independently of ubiquitination...

Breast cancer is the leading cause of cancer-related deaths in women worldwide, with the basal-like or triple-negative breast cancer (TNBC) subtype being particularly aggressive and challenging to treat. Understanding the molecular mechanisms driving the development and progression of TNBC is essential. We previously showed that WW domain-containing oxidoreductase (WWOX) is commonly inactivated in TNBC and is implicated in the DNA damage response (DDR) through ATM and ATR activation. In this study, we investigated the interplay between WWOX and BRCA1, both frequently inactivated in TNBC, on mammary tumor development and on DNA double-strand break (DSB) repair choice...

WOREE syndrome is an early infantile epileptic encephalopathy characterized by drug-resistant seizures and severe psychomotor developmental delays. We report a case of a WWOX splice-site mutation with uniparental isodisomy. A 1-year and 7-month-old girl presented with nystagmus and epileptic seizures from early infancy, with no fixation or pursuit of vision. Physical examination revealed small deformities, such as swelling of both cheeks, folded fingers, rocking feet, and scoliosis. Brain imaging revealed slight hypoplasia of the cerebrum...

INTRODUCTION: Data on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce. METHODS: We performed a genome wide association study (GWAS) to identify genes associated with survival/mortality, relapse, and severe graft-versus-host disease (sGvHD), fitting proportional hazard and subdistributional models to data of n=1,392 recipients of European ancestry from three centres. RESULTS: The single nucleotide polymorphism (SNP) rs17154454, intronic to the neuronal growth guidant semaphorin 3C gene ( SEMA3C) , was genome-wide significantly associated with event-free survival (p=7...

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[This retracts the article DOI: 10.2147/CMAR.S244573.].

Exercise training emerges as a key strategy in lifestyle modification, capable of reducing the risk of developing Alzheimer's disease (AD) due to risk factors such as age, family history, genetics and low level of education associated with AD. We aim to analyze the effect of a 14-week combined exercise training (CT) on the methylation of genes associated with AD in non-alzheimer's disease women. CT sessions lasted 60 min, occurring three times a week for 14 weeks. Forty non-Alzheimer's disease women aged 50 to 70 years (60...

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation, aberrant differentiation of keratinocytes, and dysregulated immune responses. WW domain-containing oxidoreductase (WWOX) is a non-classical tumor suppressor gene that regulates multiple cellular processes, including proliferation, apoptosis, and migration. This study aimed to explore the possible role of WWOX in the pathogenesis of psoriasis. Immunohistochemical analysis showed that the expression of WWOX was increased in epidermal keratinocytes of both human psoriatic lesions and imiquimod-induced mice psoriatic model...

Osteosarcoma is an aggressive bone tumor that primarily affects children and adolescents. This malignancy is highly aggressive, associated with poor clinical outcomes, and primarily metastasizes to the lungs. Due to its rarity and biological heterogeneity, limited studies on its molecular basis exist, hindering the development of effective therapies. The WW domain-containing oxidoreductase (WWOX) is frequently altered in human osteosarcoma. Combined deletion of Wwox and Trp53 using Osterix1-Cre transgenic mice has been shown to accelerate osteosarcoma development...

Genome association studies (GWAS) provides knowledge about the genetic architecture of beef-related traits that allow linking the target phenotype to genomic information aiding breeding decision. Thus, the present study aims to uncover the genetic mechanism involved in carcass (REA: rib eye area, BF: backfat thickness, and HCW: hot carcass weight) and meat quality traits (SF: shear-force, MARB: marbling score, and IMF: intramuscular fat content) in Nellore cattle. For this, 6910 young bulls with phenotypic information and 23,859 animals genotyped with 435 k markers were used to perform the weighted single-step GBLUP (WssGBLUP) approach, considering two iterations...

PURPOSE: Primary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive lymphoma predominantly affecting young female patients. Large-scale genomic investigations and genetic markers for risk stratification are lacking. PATIENTS AND METHODS: To elucidate the full spectrum of genomic alterations, samples from 340 patients with previously untreated PMBCL were investigated by whole-genome (n = 20), whole-exome (n = 78), and targeted (n = 308) sequencing. Statistically significant prognostic variables were identified using a multivariable Cox regression model and confirmed by L1/L2 regularized regressions...

BACKGROUND: Biallelic loss-of-function variants in WWOX cause WWOX-related epileptic encephalopathy (WOREE syndrome), which has been reported in 60 affected individuals to date. In this study, we report on an affected individual with WOREE syndrome who presented with early-onset refractory seizures and global neurodevelopmental delay and died at the age of two and a half years. METHODS: We present clinical and molecular findings in the affected individual, including biallelic pathogenic variants in the WWOX gene...

IMPORTANCE: The biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood. OBJECTIVE: To determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study collected breast tissue from women undergoing surgery for breast cancer between January 1, 1993, and December 31, 2003...

Induction of DNA damage response (DDR) to ensure accurate duplication of genetic information is crucial for maintaining genome integrity during DNA replication. Cellular senescence is a DDR mechanism that prevents the proliferation of cells with damaged DNA to avoid mitotic anomalies and inheritance of the damage over cell generations. Human WWOX gene resides within a common fragile site FRA16D that is preferentially prone to form breaks on metaphase chromosome upon replication stress. We report here that primary Wwox knockout (Wwox-/- ) mouse embryonic fibroblasts (MEFs) and WWOX-knockdown human dermal fibroblasts failed to undergo replication-induced cellular senescence after multiple passages in vitro...

INTRODUCTION: Glioblastoma (GBM) is notorious for its clinical and molecular heterogeneity, contributing to therapeutic failure and a grim prognosis. WWOX is one of the tumor suppressor genes important in nervous tissue or related pathologies, which was scarcely investigated in GBM for reliable associations with prognosis or disease progression despite known alterations. Recently, we observed a phenotypic heterogeneity between GBM cell lines (U87MG, T98G, U251MG, DBTRG-05MG), among which the anti-GBM activity of WWOX was generally corresponding, but colony growth and formation were inconsistent in DBTRG-05MG...

This study aimed to elucidate the molecular determinants influencing the response of cancer cells to alkylating agents, a major class of chemotherapeutic drugs used in cancer treatment. The study utilized data from the National Cancer Institute (NCI)-60 cell line screening program and employed a comprehensive multi-omics approach integrating transcriptomic, proteomic, metabolomic, and SNP data. Through integrated pathway analysis, the study identified key metabolic pathways, such as cysteine and methionine metabolism, starch and sucrose metabolism, pyrimidine metabolism, and purine metabolism, that differentiate drug-sensitive and drug-resistant cancer cells...

The protein WWOX was reported to be involved in cancer progression via interaction with mTOR and DNA repair pathway. We previously reported noteworthy association of some single nucleotide polymorphisms (SNPs) in mTOR and DNA repair pathways with gastric cancer (GCa) patients' survival. We hypothesized that genetic variants in WWOX gene could predict the survival of GCa patients. By extracting WWOX genetic variants from our ongoing genome-wide association study including 796 GCa patients from an Eastern Chinese population, we identified 51 out of 1913 SNPs to be significantly associated with survival of GCa patients, which passed the false positive probability tests...

OBJECTIVE: As new-generation sequencing methods develop, rare epilepsy is increasing and burdening national health systems-community building among rare epilepsies fuels collaboration, research, and resource development. Comorbidities should be carefully considered in diagnosing and treating children with rare epilepsy. This multicentric study aimed to evaluate the clinical features and comorbidities of children diagnosed with rare childhood genetic epilepsies. METHODS: This multicentric study evaluated demographics, clinical findings, neuromotor developmental progress, and concomitant comorbid diseases of childhood rare genetic epilepsies...

OBJECTIVE: Literature on the genotypic spectrum of Infantile Epileptic Spasms Syndrome (IESS) in children is scarce from developing countries. This multicentre collaboration evaluated the genotypic and phenotypic landscape of genetic IESS in Indian children. METHODS: Between January 2021 and June 2022, this cross-sectional, study was conducted at six centers in India. Children with genetically confirmed IESS, without definite structural-genetic and structural-metabolic etiology, were recruited and underwent detailed in-person assessment for phenotypic characterisation...