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Sulfatases mediate the sulfation level of cell-surface heparan sulfates to regulate signal transduction, thereby promoting cancer progression. Sulfatase activation requires a sulfatase modifying factor (SUMF) for the modification of its catalytic domain. The role of the SUMF family in urothelial carcinoma (UC) has not been adequately evaluated. In this study, we used an online database and immunohistochemistry to assess genetic changes and the mRNA and protein expression of SUMFs and related candidate targets in UC. We found that SUMF1 and SUMF2 were amplified in UC tissues. High SUMF2 mRNA levels were associated with poor overall survival (OS) and disease-free survival (DFS) in bladder UC (BLCA) from The Cancer Genome Atlas (TCGA) dataset. High SUMF2 protein levels were associated with grade (P < 0.001), T status (P = 0.01), and stage (P = 0.006) in patients with BLCA. We also examined SUMF2 expression levels in upper tract UC (UTUC). SUMF2 expression was associated with stage (P = 0.046), poor OS (P = 0.0022), and DFS (P = 0.019) in patients with UTUC. Knockdown of SUMF2 significantly reduced the migration and invasion abilities of 5637 cells. Furthermore, SUMF2 mRNA levels negatively correlated with FBXW7 mRNA levels in BLCA. The SUMF2/FBXW7 expression profile predicted the worst survival in BLCA. Taken together, SUMF2 expression is linked to unfavorable clinical outcomes in patients with UC and may serve as a useful prognostic biomarker for UC staging.
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http://dx.doi.org/10.1007/s12672-025-01859-y | DOI Listing |
Int J Biol Macromol
September 2025
Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea. Electronic addr
Mucopolysaccharidosis type II (Hunter syndrome) is a pediatric lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (I2S) gene, leading to impaired degradation and pathological accumulation of glycosaminoglycans. Mannose-6-phosphate (M6P)-containing N-glycans are critical for lysosomal targeting through mannose-6-phosphate receptors (MPRs). Idursulfase beta (IDS, Hunterase®), a recombinant human I2S produced in CHO cells, is used clinically in enzyme replacement therapy (ERT).
View Article and Find Full Text PDFHum Mutat
July 2025
Department of Molecular Mechanisms of Inherited Metabolic Disorders, Research Centre for Medical Genetics, Moscow, Russia.
Mucopolysaccharidosis Type VI (MPS VI) is a lysosomal storage disorder associated with biallelic pathogenic variants in the gene. Herein, we present three patients with biochemical and clinical pictures of MPS VI, for whom routine molecular genetic analysis using Sanger sequencing of failed to identify one or both causative variants. RNA analysis of patients' samples revealed alterations of the wild-type mRNA isoform in all cases, and one case required further analysis using whole genome sequencing.
View Article and Find Full Text PDFCarbohydr Polym
June 2025
Sorbonne Université, CNRS, Laboratoire de Biologie Intégrative des Modèles Marins, LBI2M, F-29680 Roscoff, France. Electronic address:
Carrageenans are highly diverse sulfated galactans found in red seaweeds. They play various physiological roles within macroalgae, but also serve as carbon sources for heterotrophic marine bacteria living at their surface. Carrageenan sulfatases catalyze the removal of sulfate esters from the glycans to expose the saccharide chain for further enzymatic processing.
View Article and Find Full Text PDFMol Med
May 2025
Department of Molecular Mechanisms of Inherited Metabolic Disorders, Laboratory of Experimental Gene Therapy for Inherited Metabolic Disorders, Research Centre for Medical Genetics, Moscow, Russia.
Background: Biallelic pathogenic variants in the GALNS gene lead to Mucopolysaccharidosis Type IVA (MPS IVA), a rare lysosomal storage disorder. GALNS encodes the enzyme N-acetylgalactosamine-6-sulfatase, whose deficiency causes accumulation of glycosaminoglycans and leads to a broad spectrum of clinical manifestations primarily affecting the osteoarticular system. Several studies have shown that, in 10%-15% of patients with the biochemical phenotype of MPS IVA, standard molecular genetic testing fails to identify one or both causative variants in the GALNS gene.
View Article and Find Full Text PDFGlycobiology
April 2025
Department of BioMolecular Sciences, University of Mississippi, University, MS 38677, United States.
Heparan-6-O-endosulfatase 2 (Sulf-2) is a proteoglycan enzyme that modifies sulfation of heparan sulfate proteoglycans. Dysregulation of Sulf-2 is associated with various pathological conditions, including cancer, which makes Sulf-2 a potential therapeutic target. Despite the key pathophysiological roles of Sulf-2, inhibitors remain insufficiently developed.
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