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Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer

BACKGROUND: Human replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC). METHODS: The mRNA levels of RFC4 were assessed in 30 paired p...

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Autores principales: Xiang, Jun, Fang, Lekun, Luo, Yanxin, Yang, Zuli, Liao, Yi, Cui, Ji, Huang, Meijin, Yang, Zihuan, Huang, Yan, Fan, Xinjuan, Wang, Huashe, Wang, Lei, Peng, Junsheng, Wang, Jianping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256821/
https://www.ncbi.nlm.nih.gov/pubmed/25407051
http://dx.doi.org/10.1186/s12967-014-0320-0
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author Xiang, Jun
Fang, Lekun
Luo, Yanxin
Yang, Zuli
Liao, Yi
Cui, Ji
Huang, Meijin
Yang, Zihuan
Huang, Yan
Fan, Xinjuan
Wang, Huashe
Wang, Lei
Peng, Junsheng
Wang, Jianping
author_facet Xiang, Jun
Fang, Lekun
Luo, Yanxin
Yang, Zuli
Liao, Yi
Cui, Ji
Huang, Meijin
Yang, Zihuan
Huang, Yan
Fan, Xinjuan
Wang, Huashe
Wang, Lei
Peng, Junsheng
Wang, Jianping
author_sort Xiang, Jun
collection PubMed
description BACKGROUND: Human replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC). METHODS: The mRNA levels of RFC4 were assessed in 30 paired primary CRC tissues and matched normal colonic tissues by quantitative PCR. The protein expression levels of RFC4 were evaluated by western blotting (n = 16) and immunohistochemistry (IHC; n = 49), respectively. Clinicopathological features and survival data were correlated with the expression of RFC4 by IHC analysis in a tissue microarray comprising 331 surgically resected CRC. The impact of RFC4 on cell proliferation and the cell cycle was assessed using CRC cell lines. RESULTS: RFC4 expression was significantly increased in CRC specimens as compared to adjacent normal colonic tissues (P <0.05). High levels of RFC4, determined on a tissue microarray, were significantly associated with differentiation, an advanced stage by the Tumor-Node-Metastasis (TNM) staging system, and a poor prognosis, as compared to low levels of expression (P <0.05). However, in multivariate analysis, RFC4 was not an independent predictor of poor survival for CRC. In vitro studies, the loss of RFC4 suppressed CRC cell proliferation and induced S-phase cell cycle arrest. CONCLUSION: RFC4 is frequently overexpressed in CRC, and is associated with tumor progression and worse survival outcome. This might be attributed to the regulation of CRC cell proliferation and cell cycle arrest by RFC4. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0320-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-42568212014-12-05 Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer Xiang, Jun Fang, Lekun Luo, Yanxin Yang, Zuli Liao, Yi Cui, Ji Huang, Meijin Yang, Zihuan Huang, Yan Fan, Xinjuan Wang, Huashe Wang, Lei Peng, Junsheng Wang, Jianping J Transl Med Research BACKGROUND: Human replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC). METHODS: The mRNA levels of RFC4 were assessed in 30 paired primary CRC tissues and matched normal colonic tissues by quantitative PCR. The protein expression levels of RFC4 were evaluated by western blotting (n = 16) and immunohistochemistry (IHC; n = 49), respectively. Clinicopathological features and survival data were correlated with the expression of RFC4 by IHC analysis in a tissue microarray comprising 331 surgically resected CRC. The impact of RFC4 on cell proliferation and the cell cycle was assessed using CRC cell lines. RESULTS: RFC4 expression was significantly increased in CRC specimens as compared to adjacent normal colonic tissues (P <0.05). High levels of RFC4, determined on a tissue microarray, were significantly associated with differentiation, an advanced stage by the Tumor-Node-Metastasis (TNM) staging system, and a poor prognosis, as compared to low levels of expression (P <0.05). However, in multivariate analysis, RFC4 was not an independent predictor of poor survival for CRC. In vitro studies, the loss of RFC4 suppressed CRC cell proliferation and induced S-phase cell cycle arrest. CONCLUSION: RFC4 is frequently overexpressed in CRC, and is associated with tumor progression and worse survival outcome. This might be attributed to the regulation of CRC cell proliferation and cell cycle arrest by RFC4. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0320-0) contains supplementary material, which is available to authorized users. BioMed Central 2014-11-19 /pmc/articles/PMC4256821/ /pubmed/25407051 http://dx.doi.org/10.1186/s12967-014-0320-0 Text en © Xiang et al.; licensee BioMed Central Ltd. 2014 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
Xiang, Jun
Fang, Lekun
Luo, Yanxin
Yang, Zuli
Liao, Yi
Cui, Ji
Huang, Meijin
Yang, Zihuan
Huang, Yan
Fan, Xinjuan
Wang, Huashe
Wang, Lei
Peng, Junsheng
Wang, Jianping
Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer
title Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer
title_full Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer
title_fullStr Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer
title_full_unstemmed Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer
title_short Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer
title_sort levels of human replication factor c4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256821/
https://www.ncbi.nlm.nih.gov/pubmed/25407051
http://dx.doi.org/10.1186/s12967-014-0320-0
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