Identification of Novel Proteins Interacting with Vascular Endothelial Growth Inhibitor 174 in Renal Cell Carcinoma

Background/Aim: Vascular endothelial growth inhibitor (VEGI) is a multipotential cytokine that plays a role in regulating immunity, anti-angiogenesis, and inhibiting tumor growth. However, the proteins that interact with it are still unknown. In the present study, we examined the proteins that interact with VEGI174 and their expression in renal cell carcinoma (RCC). Materials and Methods: The proteins that interact with VEGI174 were identified using western blot, pull-down assay, and mass spectrometry. The expressions of VEGI174 and the interacting proteins were examined in RCC and were compared to normal renal tissues using immunohistochemical staining and RNA-seq respectively. Results: The results of the mass spectrometric analysis showed that ACLY, ENO1, ZIK1, AKR1C3, and MYC may interact with VEGI174. When compared to the TCGA database, the expression level of VEGI174 in RCC was lower than that in normal kidney using RNAseq (p<0.001). The expression levels of ACLY, ENO1, ZIK1, AKR1C3 and MYC in RCC were higher than those in normal kidney (p<0.05, all of above factors). Moreover, immunochemical staining results also showed that the expression levels of AKR1C3 in RCC were significantly higher those that in normal kidney (p<0.001) and was also positively correlated with higher RCC stage and grade. Conclusion: Taken together, our findings showed that VEGI174 may interact with ACLY, ENO1, ZIK1, AKR1C3, and MYC. The expression of ACLY, ENO1, AKR1C3 and MYC is increased in RCC. AKR1C3 was a new factor that may correlate with the progression of RCC. The results indicated that VEGI174 has more functions than we currently know in the development and progression of RCC.National Natural Science Foundation of China [81372138]; Cancer Research WalesCPCI-S(ISTP)84379-43883