Enhancer of zeste homolog 2 (EZH2) serves as the enzymatic catalytic subunit of the polycomb repressive complex 2 (PRC2), which is capable of modifying the expression of downstream target genes through the trimethylation of Lys-27 on histone 3 (H3K27me3). In addition to its role in H3K27me3 modification, EZH2 may influence gene expression through alternative mechanisms. The involvement of EZH2 in cellular processes such as proliferation, apoptosis, and senescence has been established. Its significant contributions to the pathophysiology of cancer have garnered considerable attention. Consequently, pursuing EZH2 as a target for cancer therapy has become a prominent area of research, leading to the development of various EZH2 inhibitors. A growing number of efforts are being made to investigate the possible application of small interfering RNA (siRNA) in medical applications after the practical application of this technique to decrease gene expression in various research models. Pharmacological inhibition of EZH2 induces apoptosis in cancer cells, while siRNA-mediated downregulation of EZH2 suppresses cancer cell growth. The cell cycle is modulated by siRNA-induced suppression of EZH2, yet its precise cause is unclear. Furthermore, inadequate research has been done on the signaling route affecting cancer cells' cell cycle following EZH2 suppression with siRNA. Investigating the molecular basis of EZH2 siRNA's anticancer activity will aid in developing fresh methods for identifying, managing, and preventing cancer.
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http://dx.doi.org/10.1007/s00210-025-03883-9 | DOI Listing |
J Cell Mol Med
March 2025
Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
Loss of RB1 function represents a defining characteristic of triple-negative breast cancer (TNBC) and is intricately associated with resistance to therapeutic interventions. In this study, we investigate the epigenetic mechanisms governing RB1 expression in TNBC. Employing a combination of bioinformatics analyses and experimental validations, we identified lysine histone methyltransferase EZH2 as a key upstream regulator of RB1 expression.
View Article and Find Full Text PDFStem Cell Res Ther
March 2025
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan, 70101, Taiwan.
Background: Microenvironmental alterations induce significant genetic and epigenetic changes in stem cells. Mitochondria, essential for regenerative capabilities, provide the necessary energy for stem cell function. However, the specific roles of histone modifications and mitochondrial dynamics in human adipose-derived stem cells (ASCs) during morphological transformations remain poorly understood.
View Article and Find Full Text PDFCancer Cell
March 2025
Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address:
Isshiki et al. and Porazzi et al. report that inhibiting enhancer of zeste homolog 1 (EZH1) and EZH2 enhances chimeric antigen receptor (CAR)/T cell receptor (TCR)-based therapies by reprogramming tumors to be more immunogenic and improving T cell phenotype and demonstrate the efficacy of this combination in preclinical models across hematologic and solid cancers.
View Article and Find Full Text PDFBest Pract Res Clin Endocrinol Metab
March 2025
Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address:
Primary hyperparathyroidism is a common endocrine disorder characterized by inappropriate elevation of parathyroid hormone and hypercalcemia. While predominantly an asymptomatic disease in Western populations, symptomatic presentations are more prevalent in Eastern countries. The molecular pathogenesis of sporadic PHPT primarily involves genetic and epigenetic alterations leading to abnormal parathyroid cell proliferation and altered calcium sensing mechanism.
View Article and Find Full Text PDFCigarette smoking is a primary cause of chronic obstructive pulmonary disease (COPD). Smokers have a higher risk of influenza-related mortality, but the underlying mechanisms remain unclear. Toll-interacting protein (TOLLIP), an immune regulator, inhibits Influenza A virus (IAV) infection, but its regulation in COPD has not been well understood.
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