Conclusions
In conclusion, these findings indicated that YTHDF3 functioned as an oncogene in osteosarcoma tumorigenesis through m6A/PGK1 manner, providing a therapeutic strategy for human osteosarcoma.
Methods
The aerobic glycolysis of osteosarcoma cells were calculated by glucose uptake, lactate production analysis, ATP analysis and metabolic flux analysis for extracellular acidification rate (ECAR). Molecular binding was identified by RIP-qPCR, RNA decay analysis.
Purpose
N6-methyladenosine (m6A) modification is a pivotal transcript chemical modification of eukaryotics, which has been identified to play critical roles on tumor metabolic reprogramming. However, the functions of m6A-reading protein YTH N6-methyladenosine RNA-binding protein 3 (YTHDF3) in osteosarcoma is still unclear. This research planned to investigate the bio-functions and mechanism in osteosarcoma tumorigenesis.
Results
Results indicated that YTHDF3 is upregulated in the osteosarcoma tissue samples and cells, and closely correlated to the poor prognosis of osteosarcoma patients. Functionally, gain and loss-of-functional assays illustrated that YTHDF3 promoted the proliferation and aerobic glycolysis of osteosarcoma cells in vitro, and accelerated the tumor growth in vivo. Mechanistically, a m6A-modified PGK1 mRNA functioned as the target of YTHDF3, and YTHDF3 enhanced the PGK1 mRNA stability via m6A-dependent manner. Conclusions: In