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Background: Abnormal hedgehog (Hh) signaling is linked to preeclampsia (PE). This study aimed to identify Hh-related diagnostic biomarkers for PE and assess the role of immune infiltration.
Methods: The PE dataset was obtained from GEO to screen DEGs. WGCNA was utilized to identify Hh pathway-related genes. Following the intersection of the two genes, key genes were screened by using LASSO, SVM-RFE, and RF. A model was constructed, with ROC applied for evaluating its performance. The ssGSEA was employed to analyze immune infiltration. Network Analyst was utilized to predict miRNA/TF targets.
Results: Six Hh-related diagnostic genes were identified (SLC20A1, GPT2, PDK4, COASY, KRT81, CD163L1). The diagnostic model showed high accuracy (AUC > 0.8) in training and validation sets. PE patients exhibited immune dysfunction, including reduced dendritic cell, macrophage, and mast cell activity. Diagnostic genes strongly correlated with immune cells. Additionally, 25 miRNAs and 34 TFs potentially regulating these genes were predicted.
Conclusions: Six potential PE diagnostic biomarkers were identified, and their immune interactions were explored. This study enhances understanding of PE pathogenesis and suggests therapeutic targets.
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http://dx.doi.org/10.1080/10641955.2025.2542869 | DOI Listing |
Bioorg Chem
September 2025
Department of Pharmacy, Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:
RET tyrosine kinase, a key regulator of cellular signaling, is abnormally activated due to mutations or fusions in various cancers, making it an important therapeutic target. Traditional multi-kinase inhibitors (MKIs, such as cabozantinib and vandetanib) exhibit significant side effects due to non-selective inhibition of targets like VEGFR, and also suffer from resistance associated with RET mutations (e.g.
View Article and Find Full Text PDFJ Cell Mol Med
September 2025
School of Life Science, Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Hepatocellular carcinoma (HCC) is one of the leading cancers worldwide, and its development is strongly associated with the tumour microenvironment, particularly fibrosis and chronic inflammation. This study aims to investigate the role of the Hedgehog (Hh) pathway, a key signalling pathway in HCC progression, in the interaction between HCC cells and monocytes, which are central players in inflammation. Using a transwell migration assay, GLI1, the downstream transcriptional effector of the Hh pathway in HCC cells, was found to promote the migration of THP-1 monocyte cells.
View Article and Find Full Text PDFDev Biol
September 2025
Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC 3800, Australia. Electronic address:
The N-glycoprotein SCUBE family (Scube1, Scube2, and Scube3) plays diverse roles in vertebrate development and disease, yet many specific functions of the three family members remain unclear. These proteins exhibit broad tissue expression patterns, exist as soluble or membrane-tethered forms, and can form homo- or heteromeric complexes with each other, exerting both short- and long-range effects. Individual functional characterisation proves challenging because overlapping expression patterns and compensatory mechanisms likely obscure specific roles.
View Article and Find Full Text PDFALTEX
August 2025
Department of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
Sonic hedgehog (SHH) is a major intercellular signaling pathway involved in the orchestration of embryogenesis, including orofacial morphogenesis. The SHH pathway is sensitive to disruption, including both genetic predisposition and chemical-induced disruption at multiple molecular targets including antagonism of the SHH signal transducer Smoothened (SMO). Here we report the adverse outcome pathway (AOP) 460 describing the linkage between antagonism of the SMO receptor, a key intermediate in the hedgehog signaling, and orofacial clefts (OFCs).
View Article and Find Full Text PDFNeural crest cells (NCCs) are a multipotent cell population that undergo specification, epithelial-to-mesenchymal transition, migration, and differentiation into a plethora of cell types. A wealth of studies across various embryonic model systems have established dogma as to the molecular mechanisms and signaling cascades that contribute to NCC development. While Wnt, FGF, and BMP signaling pathways have well-established and essential roles in several aspects of NCC development, the Hedgehog (HH) signaling pathway has received limited attention for any specific role in this process.
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