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Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma
Numb, an endocytic adaptor, is a known cell fate determinant that participates in asymmetric cell division. The present study aimed to explore the potential roles of Numb in hepatocarcinogenesis. Numb expression was investigated in hepatocellular carcinomas (HCC) with reverse transcription-quantitat...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533774/ https://www.ncbi.nlm.nih.gov/pubmed/26165304 http://dx.doi.org/10.3892/ijmm.2015.2279 |
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author | XIE, CHENGZHI LU, ZHENHUI LIU, GUOXING FANG, YU LIU, JIEFENG HUANG, ZHAO WANG, FUSHENG WU, XIAOLONG LEI, XIAOHUA LI, XIAOCHENG ZHANG, YUEMING HU, ZECHENG QIAN, KE HU, JIXIONG HUANG, SHENGFU ZHONG, DEWU XU, XUNDI |
author_facet | XIE, CHENGZHI LU, ZHENHUI LIU, GUOXING FANG, YU LIU, JIEFENG HUANG, ZHAO WANG, FUSHENG WU, XIAOLONG LEI, XIAOHUA LI, XIAOCHENG ZHANG, YUEMING HU, ZECHENG QIAN, KE HU, JIXIONG HUANG, SHENGFU ZHONG, DEWU XU, XUNDI |
author_sort | XIE, CHENGZHI |
collection | PubMed |
description | Numb, an endocytic adaptor, is a known cell fate determinant that participates in asymmetric cell division. The present study aimed to explore the potential roles of Numb in hepatocarcinogenesis. Numb expression was investigated in hepatocellular carcinomas (HCC) with reverse transcription-quantitative polymerase chain reaction and immunohistochemical examination; its association with the prognosis of HCC patients was analyzed. In addition, the effects of Numb deletion on proliferation of HCC cells and its relevant molecules were evaluated in Huh7 and HepG2 cells. Numb overexpression was observed in 62% of adjacent non-tumor tissues and 46% of tumor tissues. Overexpression of Numb in HCC was associated with histological grade, portal vein invasion and the number of tumors (P=0.001, 0.022 and 0.034 respectively). Multivariate analysis revealed that Numb expression was an independent prognostic indicator of HCC patients. Methylation of the Numb promoter contributed to hepatocarcinogenesis. In vitro assays demonstrated that Numb silencing resulted in inhibition of cell proliferation, induction of apoptosis, down-regulation of cyclin-dependent protein kinase 4 (CDK4) and S-phase kinase-associated protein 2 (SKP2), and upregulation of Bcl-2 homologous antagonist/killer (BAK) and cyclin-dependent kinase inhibitor 1 (p21). The present study suggests that downregulation of Numb inhibits colony formation and cell proliferation, induces apoptosis of HCC cells and independently predicts the poor prognosis of HCC patients. Thus, Numb has a potential role in the development and progression of HCC. |
format | Online Article Text |
id | pubmed-4533774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-45337742015-11-30 Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma XIE, CHENGZHI LU, ZHENHUI LIU, GUOXING FANG, YU LIU, JIEFENG HUANG, ZHAO WANG, FUSHENG WU, XIAOLONG LEI, XIAOHUA LI, XIAOCHENG ZHANG, YUEMING HU, ZECHENG QIAN, KE HU, JIXIONG HUANG, SHENGFU ZHONG, DEWU XU, XUNDI Int J Mol Med Articles Numb, an endocytic adaptor, is a known cell fate determinant that participates in asymmetric cell division. The present study aimed to explore the potential roles of Numb in hepatocarcinogenesis. Numb expression was investigated in hepatocellular carcinomas (HCC) with reverse transcription-quantitative polymerase chain reaction and immunohistochemical examination; its association with the prognosis of HCC patients was analyzed. In addition, the effects of Numb deletion on proliferation of HCC cells and its relevant molecules were evaluated in Huh7 and HepG2 cells. Numb overexpression was observed in 62% of adjacent non-tumor tissues and 46% of tumor tissues. Overexpression of Numb in HCC was associated with histological grade, portal vein invasion and the number of tumors (P=0.001, 0.022 and 0.034 respectively). Multivariate analysis revealed that Numb expression was an independent prognostic indicator of HCC patients. Methylation of the Numb promoter contributed to hepatocarcinogenesis. In vitro assays demonstrated that Numb silencing resulted in inhibition of cell proliferation, induction of apoptosis, down-regulation of cyclin-dependent protein kinase 4 (CDK4) and S-phase kinase-associated protein 2 (SKP2), and upregulation of Bcl-2 homologous antagonist/killer (BAK) and cyclin-dependent kinase inhibitor 1 (p21). The present study suggests that downregulation of Numb inhibits colony formation and cell proliferation, induces apoptosis of HCC cells and independently predicts the poor prognosis of HCC patients. Thus, Numb has a potential role in the development and progression of HCC. D.A. Spandidos 2015-09 2015-07-09 /pmc/articles/PMC4533774/ /pubmed/26165304 http://dx.doi.org/10.3892/ijmm.2015.2279 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles XIE, CHENGZHI LU, ZHENHUI LIU, GUOXING FANG, YU LIU, JIEFENG HUANG, ZHAO WANG, FUSHENG WU, XIAOLONG LEI, XIAOHUA LI, XIAOCHENG ZHANG, YUEMING HU, ZECHENG QIAN, KE HU, JIXIONG HUANG, SHENGFU ZHONG, DEWU XU, XUNDI Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma |
title | Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma |
title_full | Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma |
title_fullStr | Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma |
title_full_unstemmed | Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma |
title_short | Numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma |
title_sort | numb downregulation suppresses cell growth and is associated with a poor prognosis of human hepatocellular carcinoma |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533774/ https://www.ncbi.nlm.nih.gov/pubmed/26165304 http://dx.doi.org/10.3892/ijmm.2015.2279 |
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