Background: Ubiquitin-specific protease 15 (USP15) exhibits amplifications in various tumors, including gastric cancer (GC), yet its biological function and mechanisms in GC progression remain elusive.
Methods: Here, we established stable USP15 knockdown or overexpression GC cell lines and explored the potential mechanism of USP15 in GC. Besides, we also identified interacting targets of USP15.
Results: USP15 knockdown significantly impeded cell proliferation, invasion, epithelial-mesenchymal transition, and distal colonization in xenograft models, while enhancing oxaliplatin's antitumor effect. USP15 was involved in ubiquitination modification of glycolytic regulators. Silencing of USP15 suppressed glycolytic activity and impaired mitochondrial functions. Interference with USP15 expression reversed tumor progression and distal colonization in vivo. HKDC1 and IGF2BP3 were found as core interacting targets of USP15, and HKDC1 was identified as a substrate for ubiquitination modification by USP15, whereby USP15 regulated glucose metabolism activity by inhibiting the ubiquitination degradation of HKDC1.
Conclusions: Our study unveiled aberrantly high expression of USP15 in GC tissues, correlating with malignant progression and nonresponse to neoadjuvant therapy. USP15 inhibitors, if developed, could be effective in promoting chemotherapy through glucose metabolism remodeling.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334570 | PMC |
| http://dx.doi.org/10.1186/s13046-024-03152-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival.
Cell Commun Signal
January 2025
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems.
View Article and Find Full Text PDFNegative association between 15 obesity- and lipid-related indices and testosterone in adult males: a population based cross-sectional study.
Lipids Health Dis
January 2025
Department of Urology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road Jinan, Shandong, 250012, People's Republic of China.
Background: An association exists between obesity and reduced testosterone levels in males. The propose of this research is to reveal the correlation between 15 indices linked to obesity and lipid levels with the concentration of serum testosterone, and incidence of testosterone deficiency (TD) among adult American men.
Methods: The study utilized information gathered from the National Health and Nutrition Examination Survey (NHANES) carried out from 2011 to 2016.
Semaglutide and laparoscopic sleeve gastrectomy in an adolescent with congenital adrenal hyperplasia due to 21-hydroxylase: a case report.
J Med Case Rep
January 2025
Department of Surgery, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles and Keck School of Medicine of USC, Los Angeles, CA, USA.
Background: Classic congenital adrenal hyperplasia, primarily due to 21-hydroxylase deficiency, leads to impaired cortisol and aldosterone production and excess adrenal androgens. Lifelong glucocorticoid therapy is required, often necessitating supraphysiological doses in youth to manage androgen excess and growth acceleration. These patients experience higher obesity rates, hypertension, and glucose metabolism issues, complicating long-term health management.
View Article and Find Full Text PDFAssociation between triglyceride glucose index and adverse cardiovascular prognosis in patients with atrial fibrillation without diabetes: a retrospective cohort study.
Lipids Health Dis
January 2025
Department of Cardiology, West China Hospital, Sichuan University West China School of Medicine, 37 Guoxue Road, Chengdu, Sichuan, 610041, China.
Background: Atrial fibrillation (AF) is the most prevalent arrhythmia encountered in clinical practice. Triglyceride glucose index (Tyg), a convenient evaluation variable for insulin resistance, has shown associations with adverse cardiovascular outcomes. However, studies on the Tyg index's predictive value for adverse prognosis in patients with AF without diabetes are lacking.
View Article and Find Full Text PDFImpact of triglyceride-glucose index on risk of cardiovascular disease among non-diabetic hypertension patients: a 10-year prospective cohort study.
BMC Public Health
January 2025
School of Public Health, Southeast University, Nanjing. 87 Dingjiaqiao Road, Nanjing, China.
Background: Triglyceride-glucose (TyG) index was regarded as a cost-efficient and reliable clinical surrogate marker for insulin resistance (IR), which was significantly correlated with cardiovascular disease (CVD). However, the TyG index and incident CVD in non-diabetic hypertension patients remains uncertain. The aim of study was to explore the impact of TyG index level and variability on risk of CVD among non-diabetic hypertension patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!