NAT10-mediated N4-acetylcytosine modification promotes the progression of retinoblastoma by improving the HK1 mRNA stability to enhance glycolysis.

OBJECTIVE

Retinoblastoma (RB) is a type of intraocular tumor in childhood with a high lethality rate. N4-acetylcytosine (acC) modification is known to regulate multiple cancers, which is mediated by the only known acC writer N-Acetyltransferase 10 (NAT10). In this study, the authors aimed to reveal the mechanism of RB progression regulated by acC modification.

METHOD

Phenotypically, dot blot assay and quantitative real-time PCR were used to detect the acC levels and NAT10 expression in clinical samples and RB cell lines. Then, NAT10 was knocked down to assess its effect on glycolysis. Mechanically, RNA immunoprecipitation assay, immunofluorescence assay, and dual luciferase report were used to explore the mRNA modified by NAT10-mediated acC modification. Mice xenograft model was used to determine the effect of NAT10 on tumor growth in vivo.

RESULTS

The present results demonstrated that the levels of acC and NAT10 were increased in cancer tissues and RB cell lines. Furthermore, NAT10 knockdown inhibited the glycolysis in RB cell lines. Moreover, the authors revealed that NAT10 knockdown decreased the acC modification and mRNA stability of HK1, while the inhibition of glycolysis by NAT10 knockdown was reversed by HK1 overexpression. Finally, NAT10 knockdown relieved the growth of tumors in mice models.

CONCLUSION

The authors illustrated that NAT10 plays an important role in the progression of RB by regulating the acC modification on HK1 mRNA and affects its stability, which may provide a novel theoretical basis for the treatment of RB.