Related Experiment Video
Updated: Jul 15, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Nicotinamide N-Methyltransferase Epigenetically Activates Fibronectin 1 Through H3K9me3 Remodeling in Clear Cell
Lingling Wang1,2,3, Yueyang Wang1,2,3, Qizheng Han3
1Department of Pathology Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is among the most prevalent malignancies of the urinary system. Patients with advanced ccRCC have poor clinical outcomes. This study aimed to investigate the role of nicotinamide N-methyltransferase (NNMT) in ccRCC. Multiomics analyses revealed aberrant expression of two enzymes in the nicotinamide metabolic pathway, both of which are associated with poor prognosis, with NNMT exhibiting the most pronounced alteration. NNMT modulation per se induces a malignant phenotype, irrespective of substrate or product supplementation. Mechanistically, using western blotting and chromatin immunoprecipitation assays, we demonstrated that NNMT decreases S-adenosylmethionine, thereby reducing histone H3 lysine 9 trimethylation (H3K9me3) at the fibronectin 1 (FN1) promoter and activating FN1 transcription. Exogenous FN1 rescued the migration and invasion in NNMT knockout cells. In clinical specimens, NNMT expression levels were markedly elevated in tumor tissues and correlated with tumor stage. NNMT inhibitor suppressed FN1 expression and tumor progression both in vitro and in vivo. Collectively, our findings establish NNMT as a pivotal epigenetic regulator that drives ccRCC progression through extracellular matrix remodeling, providing novel early-stage diagnostic and therapeutic strategies for ccRCC.
Related Concept Videos
Mitogens and the Cell Cycle
Abnormal Proliferation
Epigenetic Regulation
X-chromosome...
Epigenetic Regulation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Fibronectins Connect Cells with ECM
Both proteoglycans and collagen are attached to fibronectin proteins, which, in turn, are attached to integrin proteins. These integrin proteins interact with transmembrane...