SNORD46 stabilized by SRSF10 regulating lipid metabolism and cell proliferation of glioma cells via mediating FOXO4 2’-O-methylation

The most common primary malignant tumor of the central nervous system is glioma. One of the key features of malignant tumors is energy reprogramming, which involves changes in lipid metabolism. The objective of our study was to investigate the role of SRSF10, SNORD46, FTSJ3, and FOXO4 in regulating lipid metabolism and proliferation of glioma cells. Our findings revealed a significant increase in the expression of SRSF10, SNORD46, and FTSJ3 in glioma tissues and cells. Knockdown of SRSF10 and SNORD46 led to a reduction in both glioma cell proliferation and lipid metabolism. Furthermore, we discovered that SRSF10 enhanced the stability of SNORD46 by directly binding to it. The study revealed that FTSJ3 functions as a 2’-O-methylation transferase, while SNORD46 downregulated FOXO4 expression by promoting its 2’-O-methylation via FTSJ3. Additionally, FOXO4 suppressed lipid metabolism and cell proliferation in glioma cells by binding to the promoter regions of target genes ACLY and FASN and inhibiting transcription. Furthermore, SRSF10 stabilized SNORD46, which enhanced the SRSF10/SNORD46/FTSJ3/FOXO4 signaling pathway's role as a crucial regulator of glioma cell proliferation and lipid metabolism, presenting potential therapeutic targets for glioma treatment.