Ubiquitination and deubiquitination are important mechanisms to maintain normal physiological activities, and their disorders or imbalances can lead to various diseases. As a subgroup of deubiquitinases (DUBs), the ubiquitin-specific peptidase (USP) family is closely related to many biological processes. USP53, one of the family members, is widely expressed in human tissues and participates in a variety of life activities, such as cell apoptosis, nerve transmission, and bone remodeling. Mutations in the USP53 gene can cause cholestasis and deafness and may also be a potential cause of schizophrenia. Knockout of USP53 can alleviate neuropathic pain induced by chronic constriction injury. Loss of USP53 up-regulates RANKL expression, promotes the cytogenesis and functional activity of osteoclasts, and triggers osteodestructive diseases. USP53 plays a tumor-suppressive role in lung cancer, renal clear cell carcinoma, colorectal cancer, liver cancer, and esophageal cancer but reduces the radiosensitivity of cervical cancer and esophageal cancer to induce radioresistance. Through the in-depth combination of literature and bioinformatics, this review suggested that USP53 may be a good potential biomarker or therapeutic target for diseases.
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http://dx.doi.org/10.2174/0113892037292440240518194922 | DOI Listing |
J Clin Invest
January 2025
Center for Inherited Myology Research, Virginia Commonwealth University, Richmond, United States of America.
Background: Myotonic dystrophy type 1 (DM1) is a multisystemic, CTG repeat expansion disorder characterized by a slow, progressive decline in skeletal muscle function. A biomarker correlating RNA mis-splicing, the core pathogenic disease mechanism, and muscle performance is crucial for assessing response to disease-modifying interventions. We evaluated the Myotonic Dystrophy Splice Index (SI), a composite RNA splicing biomarker incorporating 22 disease-specific events, as a potential biomarker of DM1 muscle weakness.
View Article and Find Full Text PDFMol Cancer Res
January 2025
Fox Chase Cancer Center, Philadelphia, PA, United States.
Breast cancers of the IntClust-2 type, characterized by amplification of a small portion of chromosome 11, have a median survival of only five years. Several cancer-relevant genes occupy this portion of chromosome 11, and it is thought that overexpression of a combination of driver genes in this region is responsible for the poor outcome of women in this group. In this study we used a gene editing method to knock out, one by one, each of 198 genes that are located within the amplified region of chromosome 11 and determined how much each of these genes contributed to the survival of breast cancer cells.
View Article and Find Full Text PDFClin Cancer Res
January 2025
Bristol-Myers Squibb (United States), Summit, New Jersey, United States.
Purpose: Orvacabtagene autoleucel (orva-cel; JCARH125), a CAR T-cell therapy targeting B-cell maturation antigen (BCMA), was evaluated in relapsed/refractory multiple myeloma (RRMM) patients in the EVOLVE phase 1/2 study (NCT03430011). We applied a modified piecewise model to characterize orva-cel transgene kinetics and assessed the impact of various covariates on its pharmacokinetics (PK).
Experimental Design: The population PK analysis included 159 patients from the EVOLVE study.
Clin Cancer Res
January 2025
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
Purpose: Renal medullary carcinoma (RMC) is a highly aggressive malignancy defined by the loss of the SMARCB1 tumor suppressor. It mainly affects young individuals of African descent with sickle cell trait, and it is resistant to conventional therapies used for other renal cell carcinomas. This study aimed to identify potential biomarkers for early detection and disease monitoring of RMC.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
Purpose: To investigate the presence of uridine-5'-triphosphate (UTP)-activated P2Y1-like nucleotide receptors (P2Y2R, P2Y4R, and P2Y6R) in conjunctival goblet cells (CGCs) and determine if they increase intracellular Ca2+ concentration ([Ca2+]i) and induce mucin secretion.
Methods: Adult, male rat conjunctiva was used for culture of CGCs. To investigate the expression of P2YRs, mRNA was extracted from CGCs and used for reverse transcription PCR (RT-PCR) with commercially obtained primers specific to P2Y2R, P2Y4R, and P2Y6R.
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