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Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer

BACKGROUND: Telomerase is activated in oncogenesis, which confers an immortal phenotype to cancer cells. The AAA + ATPase Reptin is required for telomerase biogenesis by maintaining telomerase RNA (hTER) stability and is aberrantly expressed in certain cancers. Given its role in chromatin remodeling...

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Autores principales: Li, Wenjuan, Zeng, Jiping, Li, Qiao, Zhao, Li, Liu, Tiantian, Björkholm, Magnus, Jia, Jihui, Xu, Dawei
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887797/
https://www.ncbi.nlm.nih.gov/pubmed/20509972
http://dx.doi.org/10.1186/1476-4598-9-132
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author Li, Wenjuan
Zeng, Jiping
Li, Qiao
Zhao, Li
Liu, Tiantian
Björkholm, Magnus
Jia, Jihui
Xu, Dawei
author_facet Li, Wenjuan
Zeng, Jiping
Li, Qiao
Zhao, Li
Liu, Tiantian
Björkholm, Magnus
Jia, Jihui
Xu, Dawei
author_sort Li, Wenjuan
collection PubMed
description BACKGROUND: Telomerase is activated in oncogenesis, which confers an immortal phenotype to cancer cells. The AAA + ATPase Reptin is required for telomerase biogenesis by maintaining telomerase RNA (hTER) stability and is aberrantly expressed in certain cancers. Given its role in chromatin remodeling and transcription regulation, we determined the effect of Reptin on the transcription of the telomerase reverse transcriptase (hTERT) gene, a key component of the telomerase complex and its expression in gastric cancer. RESULTS: Knocking down Reptin or its partner Pontin using small interfering RNA in gastric and cervical cancer cells led to significant decreases in hTERT mRNA, but hTERT promoter activity was inhibited in only Reptin-depleted cells. Reptin interacted with the c-MYC oncoprotein and its stimulatory effect on the hTERTpromoter was significantly dependent on functional E-boxes in the promoter. Moreover, Reptin bound to the hTERT proximal promoter and the loss of the Reptin occupancy led to dissociation of c-MYC from the hTERT promoter in Reptin-depleted cells. Reptin inhibition dramatically impaired clonogenic potential of gastric cancer cells by inducing cell growtharrest and over-expression of Reptin was observed in primary gastric cancer specimens. CONCLUSIONS: The hTERT gene is a direct target of Reptin, and hTERT transcription requires constitutive expression of Reptin and its cooperation with c-MYC. Thus, Reptin regulates telomerase at two different levels. This finding, together with the requirementof Reptin for the clonogenic potential of cancer cells and its over-expression in gastriccancer and other solid tumors, suggests that Reptin may be a putative therapeutic target.
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spelling pubmed-28877972010-06-19 Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer Li, Wenjuan Zeng, Jiping Li, Qiao Zhao, Li Liu, Tiantian Björkholm, Magnus Jia, Jihui Xu, Dawei Mol Cancer Research BACKGROUND: Telomerase is activated in oncogenesis, which confers an immortal phenotype to cancer cells. The AAA + ATPase Reptin is required for telomerase biogenesis by maintaining telomerase RNA (hTER) stability and is aberrantly expressed in certain cancers. Given its role in chromatin remodeling and transcription regulation, we determined the effect of Reptin on the transcription of the telomerase reverse transcriptase (hTERT) gene, a key component of the telomerase complex and its expression in gastric cancer. RESULTS: Knocking down Reptin or its partner Pontin using small interfering RNA in gastric and cervical cancer cells led to significant decreases in hTERT mRNA, but hTERT promoter activity was inhibited in only Reptin-depleted cells. Reptin interacted with the c-MYC oncoprotein and its stimulatory effect on the hTERTpromoter was significantly dependent on functional E-boxes in the promoter. Moreover, Reptin bound to the hTERT proximal promoter and the loss of the Reptin occupancy led to dissociation of c-MYC from the hTERT promoter in Reptin-depleted cells. Reptin inhibition dramatically impaired clonogenic potential of gastric cancer cells by inducing cell growtharrest and over-expression of Reptin was observed in primary gastric cancer specimens. CONCLUSIONS: The hTERT gene is a direct target of Reptin, and hTERT transcription requires constitutive expression of Reptin and its cooperation with c-MYC. Thus, Reptin regulates telomerase at two different levels. This finding, together with the requirementof Reptin for the clonogenic potential of cancer cells and its over-expression in gastriccancer and other solid tumors, suggests that Reptin may be a putative therapeutic target. BioMed Central 2010-05-30 /pmc/articles/PMC2887797/ /pubmed/20509972 http://dx.doi.org/10.1186/1476-4598-9-132 Text en Copyright ©2010 Li 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
Li, Wenjuan
Zeng, Jiping
Li, Qiao
Zhao, Li
Liu, Tiantian
Björkholm, Magnus
Jia, Jihui
Xu, Dawei
Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer
title Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer
title_full Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer
title_fullStr Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer
title_full_unstemmed Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer
title_short Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer
title_sort reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887797/
https://www.ncbi.nlm.nih.gov/pubmed/20509972
http://dx.doi.org/10.1186/1476-4598-9-132
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