An analysis of genes possibly regulated by miR-181a-2* was carried out and, amongst these, an inverse correlation of NAMPT with miR-181a-2* expression was observed, whereas, for TRAF1 and SALL1, additional regulation mechanisms involving CpG island methylation were observed. miR-181a-2* is associated with particular histological and molecular features of colorectal carcinomas within the serrated pathological pathway and might play a role in the immune responses of microsatellite instability carcinomas.
In this study, we showed that NAMPT protein expression was increased in subjects with rectal localization compared with those with colon localization, and NAMPT was a poor prognostic marker for the overall survival rate in patients with CRC.
Collectively, our results suggest that NAMPT-mediated upregulation of the NAD(H) pool protects cancer cells against detrimental oxidative stress and that detecting NADH fluorescence by TPEF microscopy could be a potential method for monitoring CRC progression.
Assessing functional and molecular consequences of pharmacological interference with factors of the loop, we found that inhibition of NAMPT resulted in apoptosis and reduced clonogenic growth in human BRAF-mutant colorectal cancer cell lines and patient-derived tumoroids.
High expression of NAMPT or NAPRT predicts short overall survival and disease-free survival time in CRC patients, which were further confirmed by public datasets.
Targeting of NAMPT or SIRT1 may represent novel therapeutic strategies with putative higher sensitivity of the serrated route colorectal cancer subtype.