RPL35 promotes neuroblastoma progression via the enhanced aerobic glycolysis

Neuroblastoma (NB) is an rare type of tumor that almost affects children age 5 or younger due to its rapid proliferation ability. The overall survival rate of patients with advanced NB is not satisfactory. Ribosomal proteins (RPs) play a critical role in the development and progress of cancer. However, the contribution of RPL35 in NB has not been proven. In this study, we reveal that RPL35 is upregulated in NB tissues and the upregulation of RPL35 promotes proliferation and migration of NB while RPL35 knockdown significantly restrained the proliferation of NB cells. In terms of mechanism, glycolysis was decreased and the mitochondrial respiration was increased with knockdown of RPL35 in NB cells, indicating that RPL35 function as a positive regulator in aerobic glycolysis. Importantly, our data indicated that RPL35 deficiency decreased HIF1 alpha expression both in mRNA and protein levels. Western blot analysis showed that RPL35 knockdown has a negative regulatory effect on the ERK pathway, and RPL35 modulated aerobic glycolysis in part through its regulation of the RPL35/ERK/HIF1 alpha axis. Overall, RPL35 functions as a positive regulator of aerobic glycolysis, and the RPL35/ERK/HIF1 alpha axis could be a potential therapeutic target for the therapy of NB.

Automated summary

RPL35 plays a crucial role in promoting proliferation and migration of neuroblastoma cells, and its upregulation has been linked to increased aerobic glycolysis. Knockdown of RPL35 decreases HIF1 alpha expression and negatively regulates the ERK pathway, suggesting that the RPL35/ERK/HIF1 alpha axis could be a potential therapeutic target for neuroblastoma.