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Sgo1 is a potential therapeutic target for hepatocellular carcinoma

Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation. We found that the expression of Sgo1 mRNA was relatively low in normal tissues, but was upregulated in 82% of hepatocellular carcinoma...

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Autores principales: Wang, Lyu-Han, Yen, Chia-Jui, Li, Tian-Neng, Elowe, Sabine, Wang, Wen-Ching, Wang, Lily Hui-Ching
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385833/
https://www.ncbi.nlm.nih.gov/pubmed/25638162
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author Wang, Lyu-Han
Yen, Chia-Jui
Li, Tian-Neng
Elowe, Sabine
Wang, Wen-Ching
Wang, Lily Hui-Ching
author_facet Wang, Lyu-Han
Yen, Chia-Jui
Li, Tian-Neng
Elowe, Sabine
Wang, Wen-Ching
Wang, Lily Hui-Ching
author_sort Wang, Lyu-Han
collection PubMed
description Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation. We found that the expression of Sgo1 mRNA was relatively low in normal tissues, but was upregulated in 82% of hepatocellular carcinoma (HCC), and correlated with elevated alpha-fetoprotein and early disease onset of HCC. The depletion of Sgo1 reduced cell viability of hepatoma cell lines including HuH7, HepG2, Hep3B, and HepaRG. Using time-lapse microscopy, we showed that hepatoma cells were delayed and ultimately die in mitosis in the absence of Sgo1. In contrast, cell viability and mitotic progression of immortalized cells were not significantly affected. Notably, mitotic cell death induced upon Sgo1 depletion was suppressed upon inhibitions of cyclin-dependent kinase-1 and Aurora kinase-B, or the depletion of mitotic arrest deficient-2. Thus, mitotic cell death induced upon Sgo1 depletion in hepatoma cells is mediated by persistent activation of the spindle assembly checkpoint. Together, these results highlight the essential role of Sgo1 in the maintenance of a proper mitotic progression in hepatoma cells and suggest that Sgo1 is a promising oncotarget for HCC.
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spelling pubmed-43858332015-04-14 Sgo1 is a potential therapeutic target for hepatocellular carcinoma Wang, Lyu-Han Yen, Chia-Jui Li, Tian-Neng Elowe, Sabine Wang, Wen-Ching Wang, Lily Hui-Ching Oncotarget Research Paper Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation. We found that the expression of Sgo1 mRNA was relatively low in normal tissues, but was upregulated in 82% of hepatocellular carcinoma (HCC), and correlated with elevated alpha-fetoprotein and early disease onset of HCC. The depletion of Sgo1 reduced cell viability of hepatoma cell lines including HuH7, HepG2, Hep3B, and HepaRG. Using time-lapse microscopy, we showed that hepatoma cells were delayed and ultimately die in mitosis in the absence of Sgo1. In contrast, cell viability and mitotic progression of immortalized cells were not significantly affected. Notably, mitotic cell death induced upon Sgo1 depletion was suppressed upon inhibitions of cyclin-dependent kinase-1 and Aurora kinase-B, or the depletion of mitotic arrest deficient-2. Thus, mitotic cell death induced upon Sgo1 depletion in hepatoma cells is mediated by persistent activation of the spindle assembly checkpoint. Together, these results highlight the essential role of Sgo1 in the maintenance of a proper mitotic progression in hepatoma cells and suggest that Sgo1 is a promising oncotarget for HCC. Impact Journals LLC 2015-01-06 /pmc/articles/PMC4385833/ /pubmed/25638162 Text en Copyright: © 2015 Wang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Wang, Lyu-Han
Yen, Chia-Jui
Li, Tian-Neng
Elowe, Sabine
Wang, Wen-Ching
Wang, Lily Hui-Ching
Sgo1 is a potential therapeutic target for hepatocellular carcinoma
title Sgo1 is a potential therapeutic target for hepatocellular carcinoma
title_full Sgo1 is a potential therapeutic target for hepatocellular carcinoma
title_fullStr Sgo1 is a potential therapeutic target for hepatocellular carcinoma
title_full_unstemmed Sgo1 is a potential therapeutic target for hepatocellular carcinoma
title_short Sgo1 is a potential therapeutic target for hepatocellular carcinoma
title_sort sgo1 is a potential therapeutic target for hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385833/
https://www.ncbi.nlm.nih.gov/pubmed/25638162
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