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NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer

BACKGROUND: Nasopharyngeal carcinoma associated gene 6 (NGX6) is down-regulated in most colon cancer cell lines and tumor tissues when compared with their normal tissue samples. As a novel suppress tumor gene, it could inhibit colon cancer cell growth and cell cycle progression. However, little is k...

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Autores principales: Liu, Minji, Peng, Ya, Wang, Xiaoyan, Guo, Qin, Shen, Shourong, Li, Guiyuan
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868053/
https://www.ncbi.nlm.nih.gov/pubmed/20423473
http://dx.doi.org/10.1186/1471-2407-10-160
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author Liu, Minji
Peng, Ya
Wang, Xiaoyan
Guo, Qin
Shen, Shourong
Li, Guiyuan
author_facet Liu, Minji
Peng, Ya
Wang, Xiaoyan
Guo, Qin
Shen, Shourong
Li, Guiyuan
author_sort Liu, Minji
collection PubMed
description BACKGROUND: Nasopharyngeal carcinoma associated gene 6 (NGX6) is down-regulated in most colon cancer cell lines and tumor tissues when compared with their normal tissue samples. As a novel suppress tumor gene, it could inhibit colon cancer cell growth and cell cycle progression. However, little is known about the transcriptional mechanisms controlling NGX6 gene expression. Recent findings suggest that epigenetic inactivation of multiple tumor suppressor genes plays an important role in the tumorigenesis of colorectal carcinoma (CRC). In this study, we explored the role of DNA methylation in regulation of NGX6 transcription. METHODS: In the present study, we cloned the NGX6 promoter with characteristics of a CpG island by luciferase reporter assay. Then, the CpG methylation status around the NGX6 promoter region in colon cancer cell lines and colorectal tumor tissues was examined by methylation-specific PCR and bisulfite DNA sequencing. Finally, 5-Aza-2'-deoxycytidine (5-Aza-dC) treatment was used to confirm the correlation between NGX6 promoter methylation and its gene inactivation. RESULTS: The sequence spanning positions -157 to +276 was identified as the NGX6 promoter, in which no canonical TATA boxes were found, while two CAAT boxes and GC boxes were discovered. Methylation status was observed more frequently in 40 colorectal cancer samples than in 40 adjacent normal mucosa samples (18/40 versus 7/40; P < 0.05). An analysis correlating gene methylation status with clinicopathological cancer features revealed that dense methylation of the NGX6 promoter was associated with colorectal cancer patients age (P < 0.05). Moreover, a trend was shown toward metastasis status and primary site in colorectal carcinomas with NGX6 promoter methylation (p = 0.056 and P = 0.067, respectively). In addition, 5-Aza-dC could induce NGX6 mRNA expression and NGX6 promoter demethylation in HT-29 cells. CONCLUSIONS: Down-regulation of NGX6 gene is related to the promoter methylation. DNA methylation of NGX6 promoter might be a potential molecular marker for diagnosis or prognosis, or serve as a therapeutic target.
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spelling pubmed-28680532010-05-12 NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer Liu, Minji Peng, Ya Wang, Xiaoyan Guo, Qin Shen, Shourong Li, Guiyuan BMC Cancer Research Article BACKGROUND: Nasopharyngeal carcinoma associated gene 6 (NGX6) is down-regulated in most colon cancer cell lines and tumor tissues when compared with their normal tissue samples. As a novel suppress tumor gene, it could inhibit colon cancer cell growth and cell cycle progression. However, little is known about the transcriptional mechanisms controlling NGX6 gene expression. Recent findings suggest that epigenetic inactivation of multiple tumor suppressor genes plays an important role in the tumorigenesis of colorectal carcinoma (CRC). In this study, we explored the role of DNA methylation in regulation of NGX6 transcription. METHODS: In the present study, we cloned the NGX6 promoter with characteristics of a CpG island by luciferase reporter assay. Then, the CpG methylation status around the NGX6 promoter region in colon cancer cell lines and colorectal tumor tissues was examined by methylation-specific PCR and bisulfite DNA sequencing. Finally, 5-Aza-2'-deoxycytidine (5-Aza-dC) treatment was used to confirm the correlation between NGX6 promoter methylation and its gene inactivation. RESULTS: The sequence spanning positions -157 to +276 was identified as the NGX6 promoter, in which no canonical TATA boxes were found, while two CAAT boxes and GC boxes were discovered. Methylation status was observed more frequently in 40 colorectal cancer samples than in 40 adjacent normal mucosa samples (18/40 versus 7/40; P < 0.05). An analysis correlating gene methylation status with clinicopathological cancer features revealed that dense methylation of the NGX6 promoter was associated with colorectal cancer patients age (P < 0.05). Moreover, a trend was shown toward metastasis status and primary site in colorectal carcinomas with NGX6 promoter methylation (p = 0.056 and P = 0.067, respectively). In addition, 5-Aza-dC could induce NGX6 mRNA expression and NGX6 promoter demethylation in HT-29 cells. CONCLUSIONS: Down-regulation of NGX6 gene is related to the promoter methylation. DNA methylation of NGX6 promoter might be a potential molecular marker for diagnosis or prognosis, or serve as a therapeutic target. BioMed Central 2010-04-27 /pmc/articles/PMC2868053/ /pubmed/20423473 http://dx.doi.org/10.1186/1471-2407-10-160 Text en Copyright ©2010 Liu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Minji
Peng, Ya
Wang, Xiaoyan
Guo, Qin
Shen, Shourong
Li, Guiyuan
NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer
title NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer
title_full NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer
title_fullStr NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer
title_full_unstemmed NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer
title_short NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer
title_sort ngx6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868053/
https://www.ncbi.nlm.nih.gov/pubmed/20423473
http://dx.doi.org/10.1186/1471-2407-10-160
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