Cargando…
SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma
BACKGROUND: Deregulation of microtubules and centrosome integrity is response for the initiation and progression of human cancers. Sperm-associated antigen 5 (SPAG5) is essential for the spindle apparatus organization and chromosome segregation, but its role in hepatocellular carcinoma (HCC) remains...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081940/ https://www.ncbi.nlm.nih.gov/pubmed/30089483 http://dx.doi.org/10.1186/s12943-018-0872-3 |
_version_ | 1783345736660811776 |
---|---|
author | Yang, Yu-Feng Zhang, Mei-Fang Tian, Qiu-Hong Fu, Jia Yang, Xia Zhang, Chris Zhiyi Yang, Hong |
author_facet | Yang, Yu-Feng Zhang, Mei-Fang Tian, Qiu-Hong Fu, Jia Yang, Xia Zhang, Chris Zhiyi Yang, Hong |
author_sort | Yang, Yu-Feng |
collection | PubMed |
description | BACKGROUND: Deregulation of microtubules and centrosome integrity is response for the initiation and progression of human cancers. Sperm-associated antigen 5 (SPAG5) is essential for the spindle apparatus organization and chromosome segregation, but its role in hepatocellular carcinoma (HCC) remains undefined. METHODS: The expression of SPAG5 in HCC were examined in a large cohort of patients by RT-PCR, western blot and IHC. The clinical significance of SPAG5 was next determined by statistical analyses. The biological function of SPAG5 in HCC and the underlying mechanisms were investigated, using in vitro and in vivo models. RESULTS: Here, we demonstrated that SPAG5 exhibited pro-HCC activities via the activation of PI3K/AKT signaling pathway. SPAG5 expression was increased in HCC and correlated with poor outcomes in two independent cohorts containing 670 patients. High SPAG5 expression was associated with poor tumor differentiation, larger tumor size, advanced TNM stage, tumor vascular invasion and lymph node metastasis. In vitro and in vivo data showed that SPAG5 overexpression promoted tumor growth and metastasis, whereas SPAG5 knockdown led to the opposite phenotypes. SPAG5 interacted with centrosomal protein CEP55 to trigger the phosphorylation of AKT at Ser473. Inhibition of PI3K/AKT signaling markedly attenuated SPAG5-mediated cell growth. Furthermore, SPAG5 expression was suppressed by miR-363-3p which inhibited the activity of SPAG5 mRNA 3’UTR. Ectopic expression of SPAG5 partly abolished the miR-363-3p-caused cell cycle arrest and suppression of cell proliferation and migration. CONCLUSIONS: Collectively, these findings indicate that SPAG5 serves a promising prognostic factor in HCC and functions as an oncogene via CEP55-mediated PI3K/AKT pathway. The newly identified miR-363-3p/SPAG5/CEP55 axis may represent a potential therapeutic target for the clinical intervention of HCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12943-018-0872-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6081940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60819402018-08-10 SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma Yang, Yu-Feng Zhang, Mei-Fang Tian, Qiu-Hong Fu, Jia Yang, Xia Zhang, Chris Zhiyi Yang, Hong Mol Cancer Research BACKGROUND: Deregulation of microtubules and centrosome integrity is response for the initiation and progression of human cancers. Sperm-associated antigen 5 (SPAG5) is essential for the spindle apparatus organization and chromosome segregation, but its role in hepatocellular carcinoma (HCC) remains undefined. METHODS: The expression of SPAG5 in HCC were examined in a large cohort of patients by RT-PCR, western blot and IHC. The clinical significance of SPAG5 was next determined by statistical analyses. The biological function of SPAG5 in HCC and the underlying mechanisms were investigated, using in vitro and in vivo models. RESULTS: Here, we demonstrated that SPAG5 exhibited pro-HCC activities via the activation of PI3K/AKT signaling pathway. SPAG5 expression was increased in HCC and correlated with poor outcomes in two independent cohorts containing 670 patients. High SPAG5 expression was associated with poor tumor differentiation, larger tumor size, advanced TNM stage, tumor vascular invasion and lymph node metastasis. In vitro and in vivo data showed that SPAG5 overexpression promoted tumor growth and metastasis, whereas SPAG5 knockdown led to the opposite phenotypes. SPAG5 interacted with centrosomal protein CEP55 to trigger the phosphorylation of AKT at Ser473. Inhibition of PI3K/AKT signaling markedly attenuated SPAG5-mediated cell growth. Furthermore, SPAG5 expression was suppressed by miR-363-3p which inhibited the activity of SPAG5 mRNA 3’UTR. Ectopic expression of SPAG5 partly abolished the miR-363-3p-caused cell cycle arrest and suppression of cell proliferation and migration. CONCLUSIONS: Collectively, these findings indicate that SPAG5 serves a promising prognostic factor in HCC and functions as an oncogene via CEP55-mediated PI3K/AKT pathway. The newly identified miR-363-3p/SPAG5/CEP55 axis may represent a potential therapeutic target for the clinical intervention of HCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12943-018-0872-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-08 /pmc/articles/PMC6081940/ /pubmed/30089483 http://dx.doi.org/10.1186/s12943-018-0872-3 Text en © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Yang, Yu-Feng Zhang, Mei-Fang Tian, Qiu-Hong Fu, Jia Yang, Xia Zhang, Chris Zhiyi Yang, Hong SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma |
title | SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma |
title_full | SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma |
title_fullStr | SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma |
title_full_unstemmed | SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma |
title_short | SPAG5 interacts with CEP55 and exerts oncogenic activities via PI3K/AKT pathway in hepatocellular carcinoma |
title_sort | spag5 interacts with cep55 and exerts oncogenic activities via pi3k/akt pathway in hepatocellular carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081940/ https://www.ncbi.nlm.nih.gov/pubmed/30089483 http://dx.doi.org/10.1186/s12943-018-0872-3 |
work_keys_str_mv | AT yangyufeng spag5interactswithcep55andexertsoncogenicactivitiesviapi3kaktpathwayinhepatocellularcarcinoma AT zhangmeifang spag5interactswithcep55andexertsoncogenicactivitiesviapi3kaktpathwayinhepatocellularcarcinoma AT tianqiuhong spag5interactswithcep55andexertsoncogenicactivitiesviapi3kaktpathwayinhepatocellularcarcinoma AT fujia spag5interactswithcep55andexertsoncogenicactivitiesviapi3kaktpathwayinhepatocellularcarcinoma AT yangxia spag5interactswithcep55andexertsoncogenicactivitiesviapi3kaktpathwayinhepatocellularcarcinoma AT zhangchriszhiyi spag5interactswithcep55andexertsoncogenicactivitiesviapi3kaktpathwayinhepatocellularcarcinoma AT yanghong spag5interactswithcep55andexertsoncogenicactivitiesviapi3kaktpathwayinhepatocellularcarcinoma |