Upregulation of thyroid hormone receptor interactor 13 is associated with human hepatocellular carcinoma

Ju,Linling; Li,Xuefeng; Shao,Jianguo; Lu,Rujian; Wang,Yifan; Bian,Zhaolian

doi:10.3892/or.2018.6767

Upregulation of thyroid hormone receptor interactor 13 is associated with human hepatocellular carcinoma

Authors:
- Linling Ju
- Xuefeng Li
- Jianguo Shao
- Rujian Lu
- Yifan Wang
- Zhaolian Bian
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Affiliations: Nantong Institute of Liver Disease, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu 226006, P.R. China, Department of Medical Oncology, The First Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, P.R. China, Nantong Institute of Liver Disease, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu 226006, P.R. China
Published online on: October 4, 2018 https://doi.org/10.3892/or.2018.6767
Pages: 3794-3802

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Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. Thyroid hormone receptor interactor 13 (TRIP13) has been reported to promote nonhomologous end joining (NHEJ). However, the role of TRIP13 in the molecular pathogenesis of HCC remains to be elucidated. The aim of the present study was to investigate the role and potential mechanism of TRIP13 in HCC. Real-time PCR and western blotting were used to detect the expression of TRIP13 in 47 paired HCC and adjacent liver tissues. The Cancer Genome Atlas (TCGA) database was used to collect TRIP13 expression data in HCC. Loss-of-function siRNA assays were performed to alter TRIP13 expression. Cell proliferation, migration and invasion capabilities were investigated using CCK-8, wound healing and Transwell assays, while cell cycle distribution and apoptosis were assessed using flow cytometry. The expression of TRIP13 was upregulated in HCC tissues and cell lines. We analyzed the association between TRIP13 expression and patient prognosis. Patients with higher TRIP13 expression had significantly shorter survival periods compared with patients with lower TRIP13 expression. CCK-8, wound healing and Transwell assays revealed that TRIP13 downregulation inhibited the proliferation, migration and invasion of HCC cells. TRIP13 downregulation resulted in increased apoptosis and cell cycle arrest at S-phase. Finally, we found that loss of TRIP13 reduced the expression of cellular NHEJ proteins such as KU70, KU80 and PRKDC, and these results suggest that loss of TRIP 13 impairs the NHEJ repair process in HCC cells. Collectively, these results provide evidence that TRIP13 may act as a tumor promoter during HCC development and could serve as a potential therapeutic target for this disease.

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