On December 21, 2023, teachers Yilei Ma and Xucheng Huang from the First Affiliated Hospital of Zhejiang University School of Medicine in Hangzhou, Zhejiang Province, China, published a paper titled “NNMT/1-MNA Promote Cell-Cycle Progression of Breast Cancer by Targeting UBC12/Cullin-1-Mediated Degradation of P27 Proteins” in Advanced Science (IF=15.1) online. This paper utilized the Cell Cycle Staining Kit (Catalog Number: CCS012) from Multi Sciences (Hangzhou, China)

F) cell-cycle progression was analyzed by flow cytometry in MDA-MB-231 cells and BT-549 cells transfected with two distinct NNMT specific shRNA (1# and 2#) or control shRNA, results were calculated as percentage of cells in G0/G1 phase, S phase and G2/M phase. G) flow cytometry analysis of cell-cycle progression of SKBR3 cells transfected with empty vector(SKBR3/VECTOR) or NNMT-over-expressing plasmids(SKBR3/NNMT), and MCF7 cells transfected with empty vector(MCF7/VECTOR) or NNMT-over-expressing plasmids(MCF7/NNMT), and the results were calculated as percentage of cells in G0/G1 phase, S phase and G2/M phase

This study revealed the connection between Nicotinamide N-Methyltransferase activity and cell cycle progression, indicating that 1-Methylnicotinamide may be involved in reshaping the tumor microenvironment. In this study, we found that NNMT expression in breast cancer tissues was positively correlated with tumor size, histological grade, and tumor cell proliferation, with high levels of NNMT expression predicting poorer survival rates. In vitro studies confirmed that NNMT and its metabolite 1-MNA promote the proliferation and cell cycle progression of breast cancer cells by downregulating P27 expression. Mechanistically, 1-MNA promotes the degradation of P27 protein by increasing the acetylation of Cullin-1, a prerequisite for activating the Cullin-1-RING E3 ubiquitin ligase. Further research revealed that 1-MNA directly interacts with Ubiquitin-conjugating enzyme E2 L3 protein, and 1-MNA specifically protects UBC12 from degradation in lysosomes, thereby enhancing the acetylation process. Our study identified UBC12 as an intracellular target protein of 1-MNA and demonstrated that the NNMT/1-MNA pathway promotes the progression of breast cancer by participating in acetylation-mediated degradation of P27 protein.

Multi Sciences products support scientific research

The product name Cell Cycle Staining Kit, Catalog Number: CCS012

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Reference：Ma Y, Huang X, Wang Y,et al . NNMT/1-MNA Promote Cell-Cycle Progression of Breast Cancer by Targeting UBC12/Cullin-1-Mediated Degradation of P27 Proteins. Adv Sci (Weinh). 2024 Mar;11(9):e2305907.

Original text link：https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202305907