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Background: A Disintegrin and Metallopeptidase with Thrombospondin Type 1 Motif 12 (ADAMTS12), a member of the ADAMTS family of multidomain extracellular protease enzymes, is involved in the progression of many tumors. However, a pan-cancer analysis of this gene has not yet been performed. Its role in pancreatic adenocarcinoma (PAAD) also remains unclear.
Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression data (GTEx) databases were used to analyze ADAMTS12 expression in pan-cancer. We assessed the expression, clinical characteristics, prognostic significance, copy number alteration, methylation, and mutation of ADAMTS12 and its correlation with the tumor immune microenvironment. qRT-PCR and immunohistochemistry assays were also performed to validate the expression of ADAMTS12 in PAAD.
Results: Through bioinformatics analysis and preliminary experimental verification, ADAMTS12 was found to be substantially overexpressed in PAAD. High expression level of ADAMTS12 was correlated with worse survival rates in patients with PAAD and high infiltration levels of tumor-associated macrophages, cancer-associated fibroblasts, immune checkpoint proteins, and immunosuppressive genes.
Conclusion: Our findings suggest ADAMTS12 as a potential prognostic biomarker in PAAD. Elevated ADAMTS12 expression may also indicate an immunosuppressive microenvironment.
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http://dx.doi.org/10.3389/fonc.2022.849717 | DOI Listing |
FASEB J
August 2025
Department of Orthopedics, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, People's Republic of China.
Osteoarthritis (OA) is a common joint disease, and chondrocyte extracellular matrix (ECM) degradation was closely associated with its progression. This study investigated the regulatory mechanisms of ECM degradation during OA development. A rat model of OA was established by anterior cruciate ligament transection (ACL-T) and interleukin-1 beta (IL-1β)-stimulated rat chondrocytes were used to simulate OA in vitro.
View Article and Find Full Text PDFDiscov Oncol
July 2025
Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Background: We aimed to explore the regulatory gene associated with O-GlcNAcylation in oral squamous cell carcinoma (OSCC) and the underlying mechanism.
Methods: The publicly available gene expression datasets (GSE23558 and GSE25099) were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) between tumor and controls were identified by limma package.
J Mol Cell Cardiol Plus
March 2025
Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
The physiological roles of the metalloprotease-proteoglycan ADAMTS7, a drug target in atherosclerosis and vascular restenosis, and its homolog ADAMTS12, are undefined in the cardiovascular system. The objective of the present work was to investigate their roles in mice with genetic inactivation of both proteases and in relation to the resulting valve defects, to define their proteolytic activities in the matrisome. Here, we demonstrate that and are co-expressed in heart valves and each buffers inactivation of the other by compensatory upregulation.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.
Alterations in the methylation of genetic material can influence carcinogenesis by the downregulation or overexpression of (a disintegrin-like and metalloprotease with thrombospondin motifs) protease genes. Through their proteolytic activity, these enzymes are also capable of promoting angiogenesis. Consequently, ADAMTS proteases can either facilitate or inhibit cancer progression.
View Article and Find Full Text PDFBiochem Genet
January 2025
Department of Physiology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
Although DNA methyltransferase 1 (DNMT1) and RNA editor ADAR triplications exist in Down syndrome (DS), their specific roles remain unclear. DNMT methylates DNA, yielding S-adenosine homocysteine (SAH), subsequently converted to homocysteine (Hcy) and adenosine by S-adenosine homocysteine (Hcy) hydrolase (SAHH). ADAR converts adenosine to inosine and uric acid.
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