Journal Article

Overexpression of PIN1 Enhances Cancer Growth and Aggressiveness with Cyclin D1 Induction in EBV-Associated Nasopharyngeal Carcinoma

Lun, Samantha Wei-Man, Cheung, Siu-Tim, Chow, Chit, Lo, Kwok-Wai, Cheung, Chartia Ching-Mei, Xu, Meng

2016

Overview

Nasopharyngeal carcinoma (NPC) is a peculiar Epstein Barr virus (EBV)-associated malignancy that is prevalent in South-East Asia. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) isomerizes specific phosphorylated amino acid residues, which makes it an important regulator in cell survival and apoptosis. In this study, we investigated the contribution made by PIN1 in NPC tumorigenesis and PIN1's potential role as a therapeutic target. The expression of PIN1 was examined in a panel of NPC cell lines, xenografts and primary tumors. The functional roles of PIN1 in NPC cells were elucidated by the knockdown and overexpression of PIN1 in in vitro and in vivo nude mice models by siRNA and lenti-viral transfection, respectively. The antitumor effects of the PIN1 inhibitor Juglone in NPC cells were also evaluated. We revealed the consistent overexpression of PIN1 in almost all EBV-associated NPC cell lines, xenografts and primary tumors. PIN1 suppression was capable of inhibiting cyclin D1 expression and activating caspase-3 in NPC cells. It positively regulated NPC cell proliferation, colony formation and anchorage-independent growth. The inhibition of PIN1 suppressed tumor growth in vitro and in vivo. This study demonstrates the oncogenic role of PIN1 in NPC tumorigenesis, and shows that its overexpression can enhance tumor cell growth via the upregulation of cyclinD1. Our findings inform the development of novel treatments targeting PIN1 for NPC patients.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amino acids / Animal models / Animals / Anticancer properties / Antitumor activity / Apoptosis / Biology / Biology and Life Sciences / Biotechnology / Cancer / Carcinoma - drug therapy / Carcinoma - genetics / Carcinoma - metabolism / Carcinoma - virology / Caspase / Caspase 3 - metabolism / Caspase-3 / Causes of / Cell cycle / Cell growth / Cell Line, Tumor / Cell proliferation / Cell Proliferation - drug effects / Cell Proliferation - genetics / Cell Proliferation - physiology / Cell survival / Cyclin D1 / Cyclin D1 - genetics / Cyclin D1 - metabolism / Development and progression / Drug resistance / Epstein-Barr virus / Female / Gene expression / Genetic aspects / Growth / Health aspects / HeLa Cells / Herpesvirus 4, Human - pathogenicity / Humans / Immunohistochemistry / In Vitro Techniques / In vivo methods and tests / Infections / Juglone / Laboratories / Male / Malignancy / Medicine and Health Sciences / Metastasis / Mice / Mice, Inbred BALB C / Mice, Nude / Middle Aged / Naphthoquinones - pharmacology / Naphthoquinones - therapeutic use / Nasopharyngeal cancer / Nasopharyngeal Carcinoma / Nasopharyngeal Neoplasms - drug therapy / Nasopharyngeal Neoplasms - genetics / Nasopharyngeal Neoplasms - metabolism / Nasopharyngeal Neoplasms - virology / NIMA-Interacting Peptidylprolyl Isomerase - antagonists & inhibitors / NIMA-Interacting Peptidylprolyl Isomerase - metabolism / Oncology / Pathology / Peptidylprolyl isomerase / Phosphorylation / Physiological aspects / Pin1 protein / Proteins / Research and Analysis Methods / Reverse Transcriptase Polymerase Chain Reaction / Signal Transduction - drug effects / siRNA / Throat cancer / Transfection / Tumorigenesis / Tumors / Viruses / Xenografts