TRIP6 promotes cell proliferation in hepatocellular carcinoma via suppression of FOXO3a.

Abstract

Thyroid hormone receptor-interacting protein 6 (TRIP6), a member of LIM family, acts as an adaptor protein and is overexpressed in several tumor types. However, the clinical significance and biological role of TRIP6 in HCC remains unknown. In our study, we found that TRIP6 was markedly overexpressed in HCC cells and clinical specimens compared with normal hepatocytes and adjacent non-tumor tissues. Immunohistochemical and statistical analysis showed that the expression of TRIP6 significantly correlated with HCC patients' clinical stage and poor survival. Moreover, we demonstrated that overexpressing TRIP6 significantly enhanced, whereas silencing endogenous TRIP6 inhibited, the proliferation and the anchorage-independent growth ability of HCC cells. In addition, overexpression of TRIP6 accelerated, while inhibition of TRIP6 retarded, G1-S phase transition in HCC cells. We further found that overexpression of TRIP6 increased the activation of AKT and suppressed the transactivity of FOXO3a. Meanwhile, overexpression of TRIP6 leaded to the decreased expression of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 and increased expression of the cell cycle regulator cyclin D1. While silencing TRIP6 triggered the opposite effect. Taken together, these findings showed that TRIP6 plays an important role in promoting HCC cells proliferation and may serve as a novel prognostic biomarker and therapeutic target in HCC.

• Authors: Wenhui Zhao, Yubin Dai, Ting Dai, Tian Xie, Xiaobo Su, Jing Li, Xiang Zhou, Kewei Meng, Xiaohui Zhao
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 494 Issue 3-4 Pg. 594-601 (12 16 2017) ISSN: 1090-2104 [Electronic] United States
• PMID: 29080747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Biomarkers, Tumor
• FOXO3 protein, human
• Forkhead Box Protein O3
• LIM Domain Proteins
• TRIP6 protein, human
• Transcription Factors

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Carcinoma, Hepatocellular (metabolism, mortality, pathology)
• Cell Line, Tumor
• Cell Proliferation
• China (epidemiology)
• Down-Regulation
• Female
• Forkhead Box Protein O3 (metabolism)
• Hep G2 Cells
• Humans
• Incidence
• LIM Domain Proteins (metabolism)
• Liver Neoplasms (metabolism, mortality, pathology)
• Male
• Middle Aged
• Reproducibility of Results
• Risk Factors
• Sensitivity and Specificity
• Survival Rate
• Transcription Factors (metabolism)