Abstract
BackgroundNasopharyngeal 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.MethodsThe 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.ResultsWe 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.ConclusionsThis 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.
Highlights
Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck carcinoma that arises from the epithelial cells covering the surface and lining of the nasopharynx
We revealed the consistent overexpression of prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) in almost all Epstein Barr virus (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
Summary
Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck carcinoma that arises from the epithelial cells covering the surface and lining of the nasopharynx This malignancy exhibits a distinct ethnic and geographical distribution, and is prevalent in Southern China, where almost all cases are nonkeratinizing carcinomas associated with EBV infection [1, 2]. PIN1 is a highly conserved enzyme that binds to and isomerizes specific phosphorylated serine or threonine residues preceding proline (Ser/Thr-Pro) bonds. It induces conformational changes in certain proteins that prompt changes to their properties, including catalytic activities, subcellular localization, protein–protein interactions and turnover rate [5, 6]. We investigated the contribution made by PIN1 in NPC tumorigenesis and PIN1’s potential role as a therapeutic target
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