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

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). 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. 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. 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.

Zhao Q ，Kun D ，Hong B ，Deng X ，Guo S ，Tang X ，Yang Y ，Gong K ，Li Q ，Ye L ，Jiang WG ，Zhang N ... -  《-》

The differential expression of vascular endothelial growth inhibitor isoforms, VEGI251, VEGI174 and VEGI192 in human clear-cell renal cell carcinoma.

Zhang N ，Wu P ，Wu L ，Shayiremu D ，Shan H ，Ye L ，Jiang WG ，Gong K ，Yang Y ... -  《-》

Vascular endothelial growth inhibitor 174 and its functional domains inhibit epithelial-mesenchymal transition in renal cell carcinoma cells in vitro.

Zhang N ，Hong B ，Lian W ，Zhou C ，Chen S ，Du X ，Deng X ，Duoerkun S ，Li Q ，Yang Y ，Gong K ... -  《-》

Protein of Vascular Endothelial Growth Inhibitor 174 Inhibits Epithelial-Mesenchymal Transition in Renal Cell Carcinoma In Vivo.

Vascular endothelial growth inhibitor (VEGI) is a member of the tumor necrosis factor superfamily, identified as an anti-angiogenic cytokine. However, the effect of VEGI on epithelial-mesenchymal transition (EMT) in renal cell carcinoma (RCC) is still unknown. In this study, protein VEGI174 was designed and synthesized. Renal cell carcinoma A498 cells were implanted into immune-deficient mice to establish tumor models. Two groups were included: control group treated with saline, and VEGI174-treated group. Data of tumor growth were collected every 3 to 4 days. Two weeks later, the tumor specimens were harvested for immunohistochemical staining of EMT markers (E-cadherin, N-cadherin, vimentin). Compared to the saline-treated group, the VEGI174-treated group showed significant inhibition of tumor growth (p<0.05). The expression of E-cadherin was significantly higher in the VEGI174-treated group compared to the saline-treated group (p<0.01). However, the expression of N-cadherin and vimentin were reduced in the VEGI174-treated group. Our findings indicate that VEGI174 prevents progression and tumor metastasis through inhibiting EMT in RCC in vivo. This may provide a new approach for the treatment of RCC.

Zhao Q ，Deng X ，Hong B ，Wang F ，Tang X ，Yang Y ，Gong K ，Ye L ，Jiang WG ，Zhang N ... -  《-》

Suppression of renal cell carcinoma growth in vivo by forced expression of vascular endothelial growth inhibitor.

Zhang N ，Wu P ，Shayiremu D ，Wu L ，Shan H ，Ye L ，Zhao X ，Cai J ，Jiang WG ，Gong K ，Yang Y ... -  《-》