Thyroid hormone receptor interactor 13 (TRIP13) overexpression associated with tumor progression and poor prognosis in lung adenocarcinoma

Biochem Biophys Res Commun. 2018 May 15;499(3):416-424. doi: 10.1016/j.bbrc.2018.03.129. Epub 2018 Mar 30.


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 TRIP13 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 upregulatesAktSer473 and downregulatesAktThr308/mTORSer2448activity, which suppresses accurate dsDNA break repair. TRIP13 also downregulates pro-apoptotic BadSer136 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.

Keywords: Lung adenocarcinoma; Lung cancer; TRIP13; Thyroid hormone receptor interactor 13.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics*
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Animals
  • Apoptosis / genetics
  • CRISPR-Cas Systems / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Disease Progression*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockout Techniques
  • Gene Silencing
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphorylation
  • Prognosis
  • Protein Interaction Maps
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Guide, Kinetoplastida / genetics
  • RNA, Guide, Kinetoplastida / metabolism
  • Survival Analysis
  • Up-Regulation / genetics
  • Xenograft Model Antitumor Assays


  • Cell Cycle Proteins
  • RNA, Guide
  • Proto-Oncogene Proteins c-akt
  • ATPases Associated with Diverse Cellular Activities
  • TRIP13 protein, human