Background: Ubiquitin-specific protease 22 (USP22) has been implicated in the progression of breast cancer, while its regulatory functions in triple-negative breast cancer (TNBC) have been rarely reported. This study aimed to elucidate the effect and mechanism of USP22 on the malignant phenotype of TNBC cells.
Materials And Methods: The expression of USP22, stemness genes, and EMT-related markers were analyzed by RT-qPCR and/or Western blotting. Cell stemness was determined by cell spheroid formation, flow cytometry for CD44+/CD24-, and extreme limiting dilution analysis. Cell proliferation and cisplatin (DDP) chemoresistance of TNBC cells were assessed by CCK-8 assay and xenograft model. Glycolysis was measured by Seahorse assay. The mechanism underlying the role of USP22 was explored by Co-immunoprecipitation, ubiquitination assay, and cycloheximide-chase analysis.
Results: USP22 expression was positively correlated with DDP resistance in TNBC patients and cells. The proliferation, spheroid number, CD44+/CD24- cells, the expression of stemness genes and EMT-related markers in TNBC cells were significantly elevated after USP22 was overexpressed; however, these parameters in DDP-resistant TNBC (TNBC/DDP) cells were significantly reduced after silencing USP22. USP22 overexpression enhanced the extracellular acidification rate, proliferation, spheroid number, CD44+/CD24- cell number, and the expression of stemness genes and EMT-related markers in TNBC/DDP cells, while these effects were restrained by glycolysis inhibitors. Mechanically, USP22 interacted with c-Myc to promote its stabilization by deubiquitination in TNBC cells. Silencing of USP22 increased DDP sensitivity and survival of mice bearing TNBC.
Conclusion: USP22 contributes to chemoresistance, stemness, and EMT phenotype of TNBC cells by suppressing the glycolysis via c-Myc deubiquitination.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.clbc.2022.11.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanistic exploration of Traditional Chinese Medicine regulation on tumor immune microenvironment in the treatment of triple-negative breast cancer: based on CiteSpace and bioinformatics analysis.
Front Immunol
January 2025
Department of Breast and Thyroid Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, characterized by frequent recurrence, metastasis, and poor survival outcomes despite chemotherapy-based treatments. This study aims to investigate the mechanisms by which Traditional Chinese Medicine (TCM) modulates the tumor immune microenvironment in TNBC, utilizing CiteSpace and bioinformatics analysis.
Methods: We employed CiteSpace to analyze treatment hotspots and key TCM formulations, followed by bioinformatics analysis to identify the main active components, targets, associated pathways, and their clinical implications in TNBC treatment.
Deep Learning and Radiomics in Triple-Negative Breast Cancer: Predicting Long-Term Prognosis and Clinical Outcomes.
J Multidiscip Healthc
January 2025
Department of Ultrasound, Lianyungang Traditional Chinese Medicine Hospital, Lianyungang, 222004, People's Republic of China.
Triple-negative breast cancer (TNBC) is a unique breast cancer subtype characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression in tumor cells. TNBC represents about 15% to 20% of all breast cancers and is aggressive and highly malignant. Currently, TNBC diagnosis primarily depends on pathological examination, while treatment efficacy is assessed through imaging, biomarker detection, pathological evaluation, and clinical symptom improvement.
View Article and Find Full Text PDFCDKN3 as a key regulator of G2M phase in triple-negative breast cancer: Insights from multi-transcriptomic analysis.
IUBMB Life
January 2025
Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China.
Triple-negative breast cancer (TNBC) remains a significant global health challenge, emphasizing the need for precise identification of patients with specific therapeutic targets and those at high risk of metastasis. This study aimed to identify novel therapeutic targets for personalized treatment of TNBC patients by elucidating their roles in cell cycle regulation. Using weighted gene co-expression network analysis (WGCNA), we identified 83 hub genes by integrating gene expression profiles with clinical pathological grades.
View Article and Find Full Text PDFFabrication and characterization of teriflunomide-loaded chondroitin sulfate hybridized zein nanoparticles for the management of triple negative breast cancer.
Int J Biol Macromol
January 2025
Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India. Electronic address:
The objective of this work was to explore the Teriflunomide (TFM) -loaded chondroitin sulfate hybridized zein nanoparticles (TZCNPs) for the treatment of triple-negative breast cancer (TNBC). The particle size, PDI and %EE of optimized TZCNPs was found 208.7 ± 7.
View Article and Find Full Text PDFUrchin-like magnetic nanoparticles loaded with type X collagen siRNA and Stattic to treat triple negative breast cancer under rotating magnetic field like an "enchanted micro-scalpel".
Int J Biol Macromol
January 2025
Institute for Special Environmental Biophysics, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710100, Shaanxi, PR China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518063, PR China. Electronic address:
Magnetic nanoparticles effectively target drug delivery, contrast agents, biosensors, and more. Urchin-like magnetic nanoparticles (UMN) with abundant spike-like structures exhibit superior magneto-mechanical force to destroy tumor cells compared with other shapes of magnetic nanoparticles. However, when cell contents are released from tumor cells induced by magneto-mechanical force, they can act on surrounding tumor cells to facilitate tumor development.
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!