RNAseq highlights the role of Sirt2 in protecting neuronal cell from cisplatin-treated injury

Background: Cisplatin is a common and effective chemotherapeutic agent used to treat various cancers. However, it has a dose-limiting effect, resulting in chemotherapy-induced peripheral neuropathy (CIPN), which could result in treatment withdrawal or mortality. As previously demonstrated by our lab and outside data, overexpression of Sirt2 can improve neuropathy, though the mechanism is still unclear.Results: Here, RNAseq is used to further explore the role of Sirt2 under varying treatment conditions and discuss the potential mechanisms of these observations. Notably, when comparing Sirt2 knockout cells (Sirt2/KO) with cells in which Sirt2 was knocked out and subsequently rescued (Sirt2/Res), the latter manifested 323 up-expressed genes and 277 down-expressed genes. Pathway analysis suggested several pathways are involved, such as the MAPK pathway, TNF pathway, and Cytokine-cytokine interaction pathway. After treatment with cisplatin, the differentially expressed genes varied dramatically. Sirt2 KO/Res gene expression changed for 227 genes while Sirt2/KO gene expression changed for 783 genes after the treatment of cisplatin, 138 of these genes overlapped between the two different genotypes after cisplatin treatment. Pathway analysis also showed that the Sirt2/KO would affect classic pathways, such as p53, ECM-receptor interaction, and Cytokine-cytokine receptor interaction after cisplatin treatment.Conclusions: This research successfully demonstrated that different Sirt2 expression in 50B11 cells leads to a significant change in downstream gene expression. Sirt2 is also a key player in cisplatin sensitivity. In light of this, we propose immune-related function, oxidative stress, and calcium channel activity could be responsible for changes in gene expression.