PIN1 in hepatocellular carcinoma is associated with TP53 gene status

Bae,Jun Sang; Noh,Sang Jae; Kim,Kyoung Min; Jang,Kyu Yun; Park,Ho Sung; Chung,Myoung Ja; Park,Byung-Hyun; Moon,Woo Sung

doi:10.3892/or.2016.5001

PIN1 in hepatocellular carcinoma is associated with TP53 gene status

Authors:
- Jun Sang Bae
- Sang Jae Noh
- Kyoung Min Kim
- Kyu Yun Jang
- Ho Sung Park
- Myoung Ja Chung
- Byung-Hyun Park
- Woo Sung Moon
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Affiliations: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju 561-756, Republic of Korea, Department of Forensic Medicine, Chonbuk National University Medical School, Jeonju 561‑756, Republic of Korea, Department of Biochemistry, Chonbuk National University Medical School, and Research Institute for Endocrine Sciences, Jeonju 561-756, Republic of Korea
Published online on: August 4, 2016 https://doi.org/10.3892/or.2016.5001
Pages: 2405-2411

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Abstract

Phosphorylation of proteins on serine/threonine residues that precede proline (pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans isomerase PIN1. PIN1-mediated prolyl-isomerization induces cell cycle arrest and growth inhibition through the regulation of target proteins, including TP53. We examined whether PIN1 acts in a different manner according to TP53 gene status in hepatocellular carcinoma (HCC). We investigated the expression of PIN1 and TP53 proteins in 119 HCC tissue samples. We also analyzed PIN1 expression in combination with TP53 gene mutation and its correlation with the clinical outcome. In addition, we used synthetic small interfering RNA to silence PIN1 gene expression in TP53 wild-type and TP53 mutant HCC cell lines, and then evaluated cell proliferation, migration and invasion. Expression of PIN1 was strongly associated with expression of TP53 protein or TP53 mutation of HCC samples. PIN1 and TP53 expression in TP53 mutant HCC cell lines was higher than that in TP53 wild-type HCC cell lines. Silencing of PIN1 in HLE cells containing mutant TP53 significantly decreased cell proliferation, migration and invasion. In contrast to PIN1 silencing in HLE cells, PIN1 silencing in HepG2 cells containing functional wild-type TP53 resulted in enhanced tumor cell proliferation. HCC patients bearing PIN1 expression with wild-type TP53 were predicted to demonstrate favorable relapse-free survival. Our results suggest that PIN1 plays a role in cancer cell proliferation, migration and invasion in a different manner according to the TP53 gene mutation status in HCC. In particular, interaction of PIN1 with mutant TP53 can act as a tumor promoter and increase its oncogenic activities in HCC.

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