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Targeting nicotinamide N-methyltransferase decreased aggressiveness of osteosarcoma cells
E N Serritelli1, D Sartini1, R Campagna1
1Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy.
Background:
Osteosarcoma (OS) is a primary bone malignancy that mostly affects young people, characterized by high metastatic potential, and a marked chemoresistance that is responsible for disease relapse in most patients. Therefore, it is necessary to identify novel molecules to setup targeted strategies to improve the clinical outcome. The enzyme nicotinamide N-methyltransferase (NNMT) catalyses the N-methylation of nicotinamide and other analogs, playing a crucial role in the biotransformation of drugs and xenobiotics. NNMT overexpression was reported in a wide variety of cancers, and several studies demonstrated that is able to promote cell proliferation, migration and resistance to chemotherapy. The aim of this study was to explore the potential involvement of NNMT in OS.
Methods:
Immunohistochemical analyses have been performed to evaluate NNMT expression in selected OS and healthy bone tissue samples. Subsequently, OS cell lines have been transfected with vectors targeting NNMT mRNA (shRNAs) and the impact of this downregulation on migration, cell proliferation, and response to chemotherapeutic treatment was also analysed by wound healing, MTT, SRB and Trypan blue assays, respectively.
Results:
Results showed that OS samples display a significantly higher NNMT expression compared with healthy tissue. Preliminary results suggest that NNMT silencing in OS cell lines is associated to a decrease of cell proliferation and migration, as well as to enhanced sensitivity to chemotherapy. Data obtained showed that NNMT may represent an interesting marker for OS detection and a promising target for effective anti-cancer therapy.
Insights
Nicotinamide N-methyltransferase (NNMT) is overexpressed in osteosarcoma (OS) and drives cancer progression. Silencing NNMT in OS cells reduced proliferation and migration, increasing chemotherapy sensitivity.
Area of Science:
- Oncology
- Biochemistry
Background:
- Osteosarcoma (OS) is a bone cancer common in young people, often resistant to chemotherapy and prone to metastasis.
- Nicotinamide N-methyltransferase (NNMT) is an enzyme implicated in cancer cell proliferation, migration, and chemoresistance.
Purpose of the Study:
- To investigate the role of NNMT in osteosarcoma.
- To evaluate NNMT as a potential therapeutic target for OS.
Main Methods:
- Immunohistochemical analysis of NNMT expression in OS and healthy bone tissues.
- NNMT gene silencing in OS cell lines using shRNA.
- Assays for cell proliferation (MTT, SRB), migration (wound healing), and viability (Trypan blue).
Main Results:
- NNMT expression is significantly higher in OS tissues compared to healthy tissues.
- NNMT silencing reduced OS cell proliferation and migration.
- NNMT downregulation enhanced OS cell sensitivity to chemotherapy.
Conclusions:
- NNMT is a promising biomarker for osteosarcoma detection.
- Targeting NNMT may offer a novel therapeutic strategy for osteosarcoma treatment.
