Objective: USP14 (Ubiquitin-specific-processing protease 14) is a deubiquitinating enzyme with oncogenic effects in oral squamous cell carcinoma (OSCC). This study aims to identify new substrates of USP14 and elucidate their role in modulating cancer stem-like cells (CSCs) in OSCC.
Materials And Methods: Bioinformatics prediction and docking were performed using UbiBrowser 2.0 and HDOCK, respectively. OSCC cell lines and patient-derived cells were used for experimental validation, employing co-immunoprecipitation, cycloheximide chase assays, and tumor sphere formation to evaluate the effects of USP14 on SOX2 stability, ubiquitination, and CSC phenotypes.
Results: USP14 upregulation was associated with worse overall survival and progression-free interval in OSCC. USP14 interacted with SOX2 with its ubiquitin carboxyl-terminal hydrolase domain. USP14 knockdown impaired SOX2 stability by increasing its polyubiquitination. Ectopic overexpression of wild-type USP14, but not the hydrolase-deficient-mutant USP14, enhanced SOX2 stability by reducing polyubiquitination. USP14 knockdown suppressed OSCC cell proliferation, colony formation, and tumor sphere formation in vitro and tumor growth in vivo. However, the reduction of CSC markers following USP14 knockdown was mitigated by overexpressing SOX2. These findings were verified in OSCC patient-derived CSC cells.
Conclusion: This study revealed a USP14-SOX2 axis regulating the CSC properties of OSCC.
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http://dx.doi.org/10.1111/odi.14896 | DOI Listing |
J Physiol Biochem
December 2024
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, 443002, China.
SOX2 overlapping transcript (SOX2-OT) is a long non-coding RNA located at chromosome 3q26.33 in humans. Convincing data confirm that SOX2-OT is evolutionarily conserved and plays a significant role in various malignant and non-malignant diseases.
View Article and Find Full Text PDFAlzheimers Res Ther
December 2024
Department of Neuroscience, Università Cattolica del Sacro Cuore, 00168, Rome, Italy.
Background: Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by the accumulation of pathological proteins and synaptic dysfunction. This study aims to investigate the molecular and functional differences between human induced pluripotent stem cells (hiPSCs) derived from patients with sporadic AD (sAD) and age-matched controls (healthy subjects, HS), focusing on their neuronal differentiation and synaptic properties in order to better understand the cellular and molecular mechanisms underlying AD pathology.
Methods: Skin fibroblasts from sAD patients (n = 5) and HS subjects (n = 5) were reprogrammed into hiPSCs using non-integrating Sendai virus vectors.
Sci Adv
December 2024
Department of Functional Genomics and Cancer, Institute of Genetics and Molecular and Cellular Biology (IGBMC), UMR7104, Centre National de la Recherche Scientifique, U1258, Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 6704 Illkirch, France.
The spatiotemporal configuration of genes with distal regulatory elements is believed to be crucial for transcriptional control, but full mechanistic understanding is lacking. We combine simultaneous live tracking of pairs of genomic loci and nascent transcripts with molecular dynamics simulations to assess the gene and its enhancer. We find that both loci exhibit more constrained mobility than control sequences due to stalled cohesin at CCCTC-binding factor sites.
View Article and Find Full Text PDFDevelopment
December 2024
Laboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
Theranostics
December 2024
Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P. R. China.
Gastric cancer (GC) ranks as the fifth leading cause of cancer mortality, with cancer stem cells (CSCs) playing a critical role in tumor progression and resistance to chemotherapy. Conventional chemotherapy often fails to effectively target these stem cells. BATF2, a tumor suppressor, is known for its role in gastric cancer, but its influence on cancer stem cell-like properties and chemotherapy response remains unclear.
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