The Apoptosis Regulator 14-3-3η and Its Potential as a Therapeutic Target in Pituitary Oncocytoma.

The 14-3-3 protein family has attracted much attention in research into the pathogenesis of human tumors because of its involvement in tumorigenesis. In previous studies, we found that 14-3-3 eta was highly expressed in pituitary oncocytoma. However, the mechanism by which 14-3-3 eta regulates tumorigenesis in pituitary oncocytoma is unclear. 14-3-3 eta-binding proteins were investigated in pituitary oncocytoma by immunoprecipitation and proteomic analysis. A total of 443 proteins were identified as 14-3-3 eta binding proteins. The interactions of 14-3-3 eta and its binding partners were identified by a network analysis using the STRING database. The network included 433 nodes and 564 edges. PRAS40 (AKT1S1) was a binding protein of 14-3-3 eta and showed experimental interactions with 14-3-3 eta in the STRING database. The combined score was 0.407, which suggested a functional link. The 443 binding proteins of 14-3-3 eta showed enriched molecular signatures in GSEA and GO analysis. PRAS40 (AKT1S1) was enriched in the mTOR signaling pathway. Western blot analysis showed that the relative expression of p-PRAS40 (T246)/PRAS40 was significantly higher in pituitary oncocytoma than in normal pituitary tissues (p < 0.05). R18, a 14-3-3 protein inhibitor, inhibited MMQ cell proliferation after treatment with 8 mu M R18 for 48 h compared to the control group (p < 0.01). These results suggest that 14-3-3 eta may be involved in promoting tumorigenesis in pituitary oncocytoma by interacting with PRAS40 (T246) via the mTOR signaling pathway.