PRMT5 regulates the NAD-SIRT1-p53 signal axis by affecting the methylation of CD38 at R58 to promote malignant tumor cell proliferation

Abstract

The cell surface receptor CD38 has NADase enzyme and cyclase activity and is necessary for immune cell activation and proliferation. CD38 is a molecular marker for hematological tumor prognosis and diagnosis; however, its role in solid tumors is unclear. This study aimed to explore the role and mechanism of CD38 in the proliferation of solid tumor cells. We found that protein arginine methyltransferase 5 (PRMT5) interacts with CD38 in solid tumor cell lines, resulting in increased levels of CD38. In addition, PRMT5 can methylate CD38 at arginine 58 (R58). Moreover, PRMT5-induced methylation of CD38 affected its enzymatic activity and the NAD level. Finally, in vitro experiments showed that PRMT5-induced methylation of regulates the activity of the CD38-NAD-SIRT1-p53-p21 signal axis to promote the proliferation of solid tumor cells. In summary, PRMT5 promotes malignant tumor cell proliferation by regulating the methylation status of CD38 in solid tumors such as cervical cancer, nasopharyngeal carcinoma, and lung cancer. CD38 R58 could be applied in the early diagnosis and clinical treatment of solid tumors.