Conclusions
Collectively, the destruction of the NSUN5/ENO3 axis prevents ccRCC growth in vivo and in vitro, and targeting this pathway may be an effective strategy against ccRCC progression.
Methods
In this study, B-mode and microflow imaging ultrasound examinations were performed to evaluate patients with ccRCC. The extracellular acidification rate test and glucose uptake and lactate production assays were used to examine the Warburg effect in ccRCC cells. Western blotting, quantitative reverse transcription polymerase chain reaction, and immunochemistry were used to detect the expression of ENO3 and NOP2/Sun RNA methyltransferase 5 (NSUN5).
Results
ENO3 upregulation in ccRCC tumor tissues was accompanied by an increase in tumor size. Importantly, ENO3 participated in the Warburg effect observed in ccRCC cells, and high levels of ENO3 indicated a poor prognosis for patients. Loss of ENO3 reduced glucose uptake, lactate production, and extracellular acidification rate as well as inhibited ccRCC cell proliferation. Furthermore, NSUN5 was involved in the ENO3-regulated Warburg effect and ccRCC cell progression. Mechanically, NSUN5 was upregulated in ccRCC tissues, and NSUN5 upregulation mediated 5-methylcytosine modification of messenger RNA (mRNA) in ccRCC cells to promote mRNA stability and ENO3 expression. Conclusions: Collectively, the destruction of the NSUN5/ENO3 axis prevents ccRCC growth in vivo and in vitro, and targeting this pathway may be an effective strategy against ccRCC progression.