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

ABSTRACT: 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? was highly expressed in pituitary oncocytoma. However, the mechanism by which 14-3-3? regulates tumorigenesis in pituitary oncocytoma is unclear. 14-3-3?-binding proteins were investigated in pituitary oncocytoma by immunoprecipitation and proteomic analysis. A total of 443 proteins were identified as 14-3-3? binding proteins. The interactions of 14-3-3? 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? and showed experimental interactions with 14-3-3? in the STRING database. The combined score was 0.407, which suggested a functional link. The 443 binding proteins of 14-3-3? 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 ?M R18 for 48 h compared to the control group (p < 0.01). These results suggest that 14-3-3? may be involved in promoting tumorigenesis in pituitary oncocytoma by interacting with PRAS40 (T246) via the mTOR signaling pathway.

SUBMITTER: Zhao S 

PROVIDER: S-EPMC6893364 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature