CCAR2 Drives Glioma Cell Survival by Positively Regulating SIRT1 and Activating the Notch1/c‐Myc Pathway

Cell cycle and apoptosis regulator 2 (CCAR2) is a transcriptional regulator involved in diverse types of cancer. However, its role in human glioma is unclear. This study aimed to investigate whether CCAR2 could function as a regulator in glioma. Database analysis results showed that CCAR2 expression was greatly higher in glioma tissues than that in control brain tissues. Besides, CCAR2 expression was upregulated in glioma cell lines. CCAR2 knockdown inhibited cell viability and proliferation and promoted apoptosis in glioma cells. The Notch1/c-Myc pathway was found to be inactivated by CCAR2 knockdown in glioma cells, while Notch1 overexpression reversed the inhibitory effect of CCAR2 knockdown on glioma cell survival. Further investigations showed that CCAR2 interacted with SIRT1 and regulated its expression. SIRT1 overexpression also attenuated the tumor-suppressing role of CCAR2 knockdown, as well as prevented CCAR2 knockdown-caused inactivation of Notch1/c-Myc pathway. Taken together, this study demonstrated that CCAR2 depletion exerted a tumor-suppressing role in glioma through regulating SIRT1-mediated Notch1/c-Myc pathway. These findings provide evidence for the therapeutic implication of CCAR2 in glioma treatment.