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Circular RNAs (circRNAs) have emerged as pivotal regulators of the Notch signaling pathway, influencing diverse pathological processes ranging from cancer to neurodegenerative disorders. This review synthesizes evidence demonstrating how circRNAs modulate Notch activity through miRNA sponging (e.g., circ-NOTCH 1 promoting gastric cancer metastasis via miR-637/apelin axis), protein interactions, and peptide encoding. Key examples of oncogenic circRNAs are circNFIX (glioma) and circ-ASH2L (pancreatic cancer), which drive tumor progression by sponging miR-34a-5p, elevating NOTCH 1 expression, and activating downstream effectors. We also discuss tissue-specific duality of circRNAs. In fact, Notch signaling exhibits context-dependent roles, with circFBXW7 suppressing NOTCH 1 in T-ALL (tumor suppressor) versus circ-NSD2 activating JAG1/NOTCH 1 in colorectal cancer (oncogene). While circRNAs like hsa_circ_0001741 show prognostic promise, challenges persist in delivery and target specificity due to miRNA pleiotropy. By integrating mechanistic insights with preclinical examples, this review highlights circRNAs as both biomarkers and therapeutic targets, urging further research to address clinical translation barriers.
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http://dx.doi.org/10.1002/ccs3.70038 | DOI Listing |
Biomed Pharmacother
September 2025
Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Laboratory of Pharmacogenomics, Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. Electronic address:
Patients with epithelial ovarian cancer (EOC) face high mortality due to late diagnosis, recurrence, metastasis, and drug resistance. The NOTCH signaling pathway plays a critical role in cancer progression. This study analyzed NOTCH pathway deregulation in EOC patients and its response to taxane treatment in vitro and in vivo.
View Article and Find Full Text PDFNeuroendocrinology
September 2025
Introduction Neuroendocrine tumors (NETs) are a rare and heterogeneous group of neoplasms with both clinical and genetic diversity. The clinical applicability of molecular profiling using liquid biopsy for identifying actionable drug targets and prognostic indicators in patients with advanced NETs remains unclear. Methods In this study, we utilized a custom-made 37 genes panel of circulating tumor DNA (ctDNA) based on next-generation sequencing (NGS) in 47 patients with advanced NETs.
View Article and Find Full Text PDFMediators Inflamm
September 2025
College of Ophthalmology and Optometry, Shandong University of Traditional Chinese Medicine, Jinan 250002, China.
Uveitis is an inflammatory eye disease, and Longdan Xiegan Decoction (LXD) has been used to treat uveitis. However, the underlying mechanisms have not fully been addressed. The present study aimed to provide new insights into LXD ameliorating inflammatory response of experimental autoimmune uveitis (EAU) and regulating T helper (Th) cell differentiation via the interaction between microRNA (miRNA) and mRNA.
View Article and Find Full Text PDFKorean J Physiol Pharmacol
September 2025
Department of Physiology & Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea.
Diabetes mellitus is a major global health concern associated with micro-and macrovascular complications. Among the diverse mechanisms that contribute to vascular dysfunction in diabetes, endothelial to mesenchymal transition (EndMT) has emerged as a key pathological process. EndMT involves the loss of endothelial cell characteristics and the acquisition of mesenchymal features, resulting in impaired endothelial function, increased fibrosis, and inflammation.
View Article and Find Full Text PDFMed
August 2025
Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece; Centre of New Biotechnologies and Precision Medicine (CNBPM), School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece. Electronic address: p
Background: Pathogenic responses against self and foreign antigens in systemic autoimmunity and infection, respectively, engage similar immunologic components, thus lacking distinguishing diagnostic biomarkers. Herein, we tested whether whole-blood transcriptome analysis discriminates autoimmune from infectious diseases.
Methods: We applied nested cross-validation methodology to tune and validate random forests, k-nearest neighbors, and support vector machines, using a new preprocessing method on 22 publicly available datasets, including 594 patients with a broad spectrum of systemic autoimmune diseases and 615 patients with diverse viral, bacterial, and parasitic infections.