NAT10 contributes to the progression of multiple myeloma through ac4C modification of GPR37.

Abstract

Background: Multiple myeloma (MM) is a malignant plasma-cell disease. Epigenetic modifications, including acetylation, are thought to contribute to tumorigenesis. N-acetyltransferase 10 (NAT10) is an important regulator of mRNA acetylation in various tumors. In this study, we explored the functions and mechanisms of action of NAT10 in MM.

Methods: The expression of G protein-coupled receptor 37 (GPR37) and NAT10 was determined by qRT-PCR and western blotting, respectively. Cell proliferation was assessed using MTT and EdU assays. Cell apoptosis and cell cycle processes were analyzed using flow cytometry. Glycolysis levels were estimated using relevant commercial kits. The relationship between GPR37 and NAT10 was analyzed using the Acetylated RNA immunoprecipitation (acRIP), RIP and Actinomycin D assays. A murine xenograft model was constructed to explore the functional roles of GPR37 and NAT10 in tumor growth in vivo.

Results: GPR37 was highly expressed in MM sera and cells. GPR37 knockdown inhibited MM cell proliferation, cell cycle, glycolysis, and immune escape and facilitated apoptosis in vitro. Mechanistically, NAT10 positively modulated GPR37 expression through the ac4C modification of GPR37 mRNA. Moreover, our results showed that NAT10 knockdown repressed MM cell proliferation, cell cycle, glycolysis, and immune escape; facilitated apoptosis in vitro and inhibited tumor growth in vivo by regulating GPR37 expression.

Conclusion: NAT10 aggravated MM malignancy by regulating GPR37 expression. These results indicate that NAT10 and GPR37 may be novel targets for MM therapy.