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EZH2 deletion does not impact acinar regeneration but restricts progression to pancreatic cancer in mice.
JCI Insight
December 2024
Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.
Enhancer of Zeste Homologue 2 (EZH2) is part of the Polycomb Repressor Complex 2, which promotes trimethylation of lysine 27 on histone 3 (H3K27me3) and genes repression. EZH2 is overexpressed in many cancers and studies in mice attributed both pro-oncogenic and tumor suppressive functions to EZH2 in pancreatic ductal adenocarcinoma (PDAC). EZH2 deletion enhances de novo KRAS-driven neoplasia following pancreatic injury, while increased EZH2 expression in PDAC patients is correlated to poor prognosis, suggesting a context-dependant effect for EZH2 in PDAC progression.
View Article and Find Full Text PDFNSUN2-Mediated R-loop Stabilization as a Key Driver of Bladder Cancer Progression and Cisplatin Sensitivity.
Cancer Lett
December 2024
Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang, 310058, China. Electronic address:
R-loops are critical structures that play pivotal roles in regulating genomic stability and modulating gene expression. This study investigates the interactions between the 5-methylcytosine (mC) methyltransferase NOP2/Sun RNA methyltransferase 2 (NSUN2) and R-loops in the transcriptional dynamics and damage repair process of bladder cancer (BCa) cells. We observed markedly elevated levels of R-loops in BCa cells relative to normal urothelial cells.
View Article and Find Full Text PDFEpigenetic Regulation of Nuclear Factor Erythroid-2-Related Factor 2 in Colorectal Cancer Cells Resistant to Ionizing Radiation.
Biomol Ther (Seoul)
January 2025
Department of Biochemistry, College of Medicine, and Jeju Natural Medicine Research Center, Jeju National University, Jeju 63243, Republic of Korea.
γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators.
View Article and Find Full Text PDFEZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis by regulating endoplasmic reticulum stress in knee osteoarthritis.
Chin Med J (Engl)
December 2024
Department of Orthopedic Surgery & Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Background: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported.
View Article and Find Full Text PDFTargeting Epigenetic Dysregulations in Head and Neck Squamous Cell Carcinoma.
J Dent Res
December 2024
Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Head and neck squamous cell carcinoma (HNSCC) is one of the deadliest human cancers, with the overall 5-year survival rate stagnating in recent decades due to the lack of innovative treatment approaches. Apart from the recently Food and Drug Administration-approved epidermal growth factor receptor inhibitor and immune checkpoint inhibitor, alternative therapeutic strategies that target epigenetic abnormalities, an emerging cancer hallmark, remain to be fully explored. A pathological epigenetic landscape, characterized by widespread reprogramming of chromatin modifications such as DNA methylation and histone modifications, which drives transcription deregulation and genome reorganization, has been extensively documented in numerous cancers, including HNSCC.
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