Anti-NNMT monoclonal antibody

Background Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders. Results This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having apvalue < 0.05. The expression profiling and the functional enrichment analysis revealed the role of these genes in cell communication, signal transduction, and immune response. The protein-protein interaction showed the functional association of the source genes (CTNNB1, NNMT, PTCH1, CALD1, CXCL14, CXCL8, and TNFAIP3) with the target proteins, such as AXIN, MAPK, IL6, STAT, APC, GSK3B, and SHH. Conclusion The integrated pathway analysis indicated the role of these genes in important physiological responses, such as cell cycle regulation, WNT, hedgehog, MAPK, and calcium signaling pathways during colorectal cancer. These pathways are involved in cell proliferation, chemotaxis, cellular growth, differentiation, tissue patterning, and cytokine production. The study shows the regulatory role of these genes in colorectal cancer and the pathways that can be effected after the dysregulation of these genes.

Nicotinamide N-methyltransferase (NNMT), which converts nicotinamide to 1-methylnicotinamide (1-MNA), is overexpressed in a variety of human cancers and serves as a potential anti-cancer target. In this study, we investigated the effect of NNMT on 5-fluorouracil (5-FU) sensitivity of colorectal cancer (CRC) cells, and the underlying mechanisms. Our results show that down-regulation of NNMT in CRC HT-29 cells diminishes 5-FU resistance, while over expression of NNMT in SW480 cells enhances it. NNMT reduces reactive oxygen species (ROS) production induced by 5-FU by increasing 1-MNA in CRC cells. The reduction in ROS leads to inactivation of the ASK1-p38 mitogen-activated protein kinase (MAPK) pathway, which reduces 5-FU-induced apoptosis. In vivo, NNMT attenuates 5-FU-induced inhibition of CRC tumor growth in nude mice. These observations suggest that NNMT and the 1-MNA it produces inhibit the ASK1-p38 MAPK pathway, resulting in increased CRC cell resistance to 5-FU.