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Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma

BACKGROUND: Karyopherin alpha 2 (KPNA2) promotes tumor growth in hepatocellular carcinoma (HCC). We aimed to determine the content and clinical significance of mechanism underlying. METHODS: The association of transcriptional factor pleomorphic adenoma gene 1 (PLAG1) with KPNA2 was explored by co-im...

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Autores principales: Hu, Zhe-yuan, Yuan, Sheng-xian, Yang, Yuan, Zhou, Wei-ping, Jiang, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122822/
https://www.ncbi.nlm.nih.gov/pubmed/25060425
http://dx.doi.org/10.1186/s13046-014-0061-1
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author Hu, Zhe-yuan
Yuan, Sheng-xian
Yang, Yuan
Zhou, Wei-ping
Jiang, Hua
author_facet Hu, Zhe-yuan
Yuan, Sheng-xian
Yang, Yuan
Zhou, Wei-ping
Jiang, Hua
author_sort Hu, Zhe-yuan
collection PubMed
description BACKGROUND: Karyopherin alpha 2 (KPNA2) promotes tumor growth in hepatocellular carcinoma (HCC). We aimed to determine the content and clinical significance of mechanism underlying. METHODS: The association of transcriptional factor pleomorphic adenoma gene 1 (PLAG1) with KPNA2 was explored by co-immunoprecipitation. In vitro gain- and loss-of-function models were established to explore the functional interaction. Clinical samples from 314 HCC patients were applied to explore the clinical significance. RESULTS: We found that PLAG1 could associate with KPNA2 and be promoted into nucleus by KPNA2. The increment of proliferative and metastatic abilities by KPNA2 over-expression can be significantly retarded by PLAG1 inhibition. The co-enrichment of KPNA2 and PLAG1 in nucleus is observed in clinical samples and can distinguish patients with the worst prognosis. The positive PLAG1 expression is an independent risk factor of recurrence free survival (HR: 1.766, 1.315-2.371; P = 0.000) and overall survival (HR: 1.589, 1.138-2.220; P = 0.007). Especially for patients with positive KPNA2 staining (N = 152), the positive PLAG1 expression is the sole risk factor for both recurrence free survival (HR: 1.749, 1.146-2.670; P = 0.010) and overall survival (HR: 1.662, 1.007-2.744; P = 0.047). CONCLUSIONS: The nuclear import of PLAG1 by KPNA2 is essential for the role of KPNA2 in HCC cells and is significant to predict poor survival of HCC patients after hepatectomy.
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spelling pubmed-41228222014-08-07 Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma Hu, Zhe-yuan Yuan, Sheng-xian Yang, Yuan Zhou, Wei-ping Jiang, Hua J Exp Clin Cancer Res Research BACKGROUND: Karyopherin alpha 2 (KPNA2) promotes tumor growth in hepatocellular carcinoma (HCC). We aimed to determine the content and clinical significance of mechanism underlying. METHODS: The association of transcriptional factor pleomorphic adenoma gene 1 (PLAG1) with KPNA2 was explored by co-immunoprecipitation. In vitro gain- and loss-of-function models were established to explore the functional interaction. Clinical samples from 314 HCC patients were applied to explore the clinical significance. RESULTS: We found that PLAG1 could associate with KPNA2 and be promoted into nucleus by KPNA2. The increment of proliferative and metastatic abilities by KPNA2 over-expression can be significantly retarded by PLAG1 inhibition. The co-enrichment of KPNA2 and PLAG1 in nucleus is observed in clinical samples and can distinguish patients with the worst prognosis. The positive PLAG1 expression is an independent risk factor of recurrence free survival (HR: 1.766, 1.315-2.371; P = 0.000) and overall survival (HR: 1.589, 1.138-2.220; P = 0.007). Especially for patients with positive KPNA2 staining (N = 152), the positive PLAG1 expression is the sole risk factor for both recurrence free survival (HR: 1.749, 1.146-2.670; P = 0.010) and overall survival (HR: 1.662, 1.007-2.744; P = 0.047). CONCLUSIONS: The nuclear import of PLAG1 by KPNA2 is essential for the role of KPNA2 in HCC cells and is significant to predict poor survival of HCC patients after hepatectomy. BioMed Central 2014-07-25 /pmc/articles/PMC4122822/ /pubmed/25060425 http://dx.doi.org/10.1186/s13046-014-0061-1 Text en Copyright © 2014 Hu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Hu, Zhe-yuan
Yuan, Sheng-xian
Yang, Yuan
Zhou, Wei-ping
Jiang, Hua
Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma
title Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma
title_full Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma
title_fullStr Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma
title_full_unstemmed Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma
title_short Pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma
title_sort pleomorphic adenoma gene 1 mediates the role of karyopherin alpha 2 and has prognostic significance in hepatocellular carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122822/
https://www.ncbi.nlm.nih.gov/pubmed/25060425
http://dx.doi.org/10.1186/s13046-014-0061-1
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