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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Endocrinol. | doi: 10.3389/fendo.2019.00797

The apoptosis regulator 14-3-3η and its potential as a therapeutic target in pituitary oncocytomas

SIDA ZHAO1, BIN LI2,  CHUZHONG LI1, HUA GAO1, YAZHOU MIAO1, YUE HE1, HONGYUN WANG1, LEI GONG1, DAN LI1 and  JIE FENG1*
  • 1Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, China
  • 2Beijing Tiantan Hospital, Capital Medical University, China

The 14-3-3 protein family has attracted much attention in the pathogenesis of human tumors because of its involvement in tumorigenesis. In previous studies, we found that 14-3-3η was highly expressed in pituitary oncocytomas. However, the mechanism by which 14-3-3η regulates tumorigenesis in pituitary oncocytomas is unclear. 14-3-3η-binding proteins were investigated in pituitary oncocytomas by immunoprecipitation and proteomic analysis. A total of 443 proteins were identified as 14-3-3η binding proteins. The interactions of 14-3-3η 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 14-3-3η and showed experimental interactions with 14-3-3η in the STRING database. The combined score was 0.407, which suggested a functional link. The 443 binding proteins of 14-3-3η showed enriched molecular signatures in the 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 oncocytomas than in normal pituitary tissues (p<0.05). R18, an 14-3-3 protein inhibitor, inhibited MMQ cell proliferation after treatment with 8 µM R18 for 48 h compared to the control group (p<0.01). These results suggest that 14-3-3η may be involved in promoting tumorigenesis in pituitary oncocytomas by interacting with PRAS40 (T246) via the mTOR signaling pathway.

Keywords: Pituitary, Adenoma - pathology, 14-3-3 eta, CoIP, coimmunoprecipitation, Mass spectrum, Proteomics, Tumor proliferation

Received: 25 Apr 2019; Accepted: 01 Nov 2019.

Copyright: © 2019 ZHAO, LI, LI, GAO, MIAO, HE, WANG, GONG, LI and FENG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. JIE FENG, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, Beijing Municipality, China, fj79330@163.com