Biochemical and Biophysical Research Communications, Vol.499, No.3, 416-424, 2018
Thyroid hormone receptor interactor 13 (TRIP13) overexpression associated with tumor progression and poor prognosis in lung adenocarcinoma
Thyroid hormone receptor interactor 13 (TRIP13) is an AAA(+)-ATPase that plays a key role in mitotic checkpoint complex inactivation and is associated with the progression of several cancers. However, its role in lung adenocarcinogenesis remains unknown. Here, we report that TRIM is highly overexpressed in multiple lung adenocarcinoma cell lines and tumor tissues. Clinically, TRIP13 expression is positively associated with tumor size, T-stage, and N-stage, and Kaplan-Meier analysis revealed that heightened TRIP13 expression is associated with lower overall survival. TRIP13 promotes lung adenocarcinoma cell proliferation, clonogenicity, and migration while inhibiting apoptosis and G2/M phase shift in vitro. Accordingly, TRIP13-silenced xenograft tumors displayed significant growth inhibition in vivo. Bioinformatics analysis demonstrated that TRIP13 interacts with a protein network associated with dsDNA break repair and PI3K/Akt signaling. TRIP13 upregulatesAkt(Ser47s) and downregulatesAk(Tmr308)/mTOR-(Ser2448)activity, which suppresses accurate dsDNA break repair. TRIP13 also downregulates pro-apoptotic Bad(Ser136) and cleaved caspase-3 while upregulating survivin. In conclusion, heightened TRIP13 expression appears to promote lung adenocarcinoma tumor progression and displays potential as a therapeutic target or biomarker for lung adenocarcinoma. (C) 2018 Elsevier Inc. All rights reserved.