We investigated the role of the WW domain-containing oxidoreductase (wwox) gene in the embryonic development of zebrafish, with particular emphasis on intracellular Ca(2+) dynamics because Ca(2+) is an important intracellular messenger. Comparisons between zebrafish wwox and human WWOX sequences identified highly conserved domain structures. wwox was expressed in developing heart tissues in the zebrafish embryo. Moreover, wwox knockdown induced pericardial edema with similarities to conditions observed in human breast cancer. The wwox knockdown embryos with the edema died within a week. High Ca(2+) levels were observed at the boundary between the edema and yolk in wwox knockdown embryos.
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http://dx.doi.org/10.7717/peerj.727 | DOI Listing |
Sci Rep
June 2024
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, Gilman Dr., La Jolla, CA, 92093, USA.
In vitro evolution and whole genome analysis has proven to be a powerful method for studying the mechanism of action of small molecules in many haploid microbes but has generally not been applied to human cell lines in part because their diploid state complicates the identification of variants that confer drug resistance. To determine if haploid human cells could be used in MOA studies, we evolved resistance to five different anticancer drugs (doxorubicin, gemcitabine, etoposide, topotecan, and paclitaxel) using a near-haploid cell line (HAP1) and then analyzed the genomes of the drug resistant clones, developing a bioinformatic pipeline that involved filtering for high frequency alleles predicted to change protein sequence, or alleles which appeared in the same gene for multiple independent selections with the same compound. Applying the filter to sequences from 28 drug resistant clones identified a set of 21 genes which was strongly enriched for known resistance genes or known drug targets (TOP1, TOP2A, DCK, WDR33, SLCO3A1).
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
June 2024
Division of Pulmonary, Critical Care, Sleep and Allergy Medicine, University of Illinois at Chicago, Chicago, Illinois, United States.
Chronic cigarette smoke exposure decreases lung expression of which is known to protect the endothelial barrier during infectious models of acute respiratory distress syndrome (ARDS). Proteomic analysis of -silenced endothelial cells (ECs) was done using tandem mass tag mass spectrometry (TMT-MS). -silenced ECs as well as those isolated from endothelial cell knockout (EC KO) mice were subjected to cyclic stretch (18% elongation, 0.
View Article and Find Full Text PDFInt J Mol Sci
December 2023
Department of Dermatology, College of Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea.
Cell Mol Life Sci
October 2023
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan.
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.
View Article and Find Full Text PDFInt J Cancer
January 2024
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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.
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