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Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis

Inactivation of tumour suppressor genes by promoter methylation plays an important role in the initiation and progression of gastric cancer (GC). Transmembrane 106A gene (TMEM106A) encodes a novel protein of previously unknown function. This study analysed the biological functions, epigenetic change...

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Autores principales: Xu, Dong, Qu, Liujing, Hu, Jia, Li, Ge, Lv, Ping, Ma, Dalong, Guo, Mingzhou, Chen, Yingyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190911/
https://www.ncbi.nlm.nih.gov/pubmed/24975047
http://dx.doi.org/10.1111/jcmm.12352
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author Xu, Dong
Qu, Liujing
Hu, Jia
Li, Ge
Lv, Ping
Ma, Dalong
Guo, Mingzhou
Chen, Yingyu
author_facet Xu, Dong
Qu, Liujing
Hu, Jia
Li, Ge
Lv, Ping
Ma, Dalong
Guo, Mingzhou
Chen, Yingyu
author_sort Xu, Dong
collection PubMed
description Inactivation of tumour suppressor genes by promoter methylation plays an important role in the initiation and progression of gastric cancer (GC). Transmembrane 106A gene (TMEM106A) encodes a novel protein of previously unknown function. This study analysed the biological functions, epigenetic changes and the clinical significance of TMEM106A in GC. Data from experiments indicate that TMEM106A is a type II membrane protein, which is localized to mitochondria and the plasma membrane. TMEM106A was down-regulated or silenced by promoter region hypermethylation in GC cell lines, but expressed in normal gastric tissues. Overexpression of TMEM106A suppressed cell growth and induced apoptosis in GC cell lines, and retarded the growth of xenografts in nude mice. These effects were associated with the activation of caspase-2, caspase-9, and caspase-3, cleavage of BID and inactivation of poly (ADP-ribose) polymerase (PARP). In primary GC samples, loss or reduction of TMEM106A expression was associated with promoter region hypermethylation. TMEM106A was methylated in 88.6% (93/105) of primary GC and 18.1% (2/11) in cancer adjacent normal tissue samples. Further analysis suggested that TMEM106A methylation in primary GCs was significantly correlated with smoking and tumour metastasis. In conclusion, TMEM106A is frequently methylated in human GC. The expression of TMEM106A is regulated by promoter hypermethylation. TMEM106A is a novel functional tumour suppressor in gastric carcinogenesis.
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spelling pubmed-41909112014-12-03 Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis Xu, Dong Qu, Liujing Hu, Jia Li, Ge Lv, Ping Ma, Dalong Guo, Mingzhou Chen, Yingyu J Cell Mol Med Original Articles Inactivation of tumour suppressor genes by promoter methylation plays an important role in the initiation and progression of gastric cancer (GC). Transmembrane 106A gene (TMEM106A) encodes a novel protein of previously unknown function. This study analysed the biological functions, epigenetic changes and the clinical significance of TMEM106A in GC. Data from experiments indicate that TMEM106A is a type II membrane protein, which is localized to mitochondria and the plasma membrane. TMEM106A was down-regulated or silenced by promoter region hypermethylation in GC cell lines, but expressed in normal gastric tissues. Overexpression of TMEM106A suppressed cell growth and induced apoptosis in GC cell lines, and retarded the growth of xenografts in nude mice. These effects were associated with the activation of caspase-2, caspase-9, and caspase-3, cleavage of BID and inactivation of poly (ADP-ribose) polymerase (PARP). In primary GC samples, loss or reduction of TMEM106A expression was associated with promoter region hypermethylation. TMEM106A was methylated in 88.6% (93/105) of primary GC and 18.1% (2/11) in cancer adjacent normal tissue samples. Further analysis suggested that TMEM106A methylation in primary GCs was significantly correlated with smoking and tumour metastasis. In conclusion, TMEM106A is frequently methylated in human GC. The expression of TMEM106A is regulated by promoter hypermethylation. TMEM106A is a novel functional tumour suppressor in gastric carcinogenesis. Blackwell Publishing Ltd 2014-08 2014-06-28 /pmc/articles/PMC4190911/ /pubmed/24975047 http://dx.doi.org/10.1111/jcmm.12352 Text en © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Xu, Dong
Qu, Liujing
Hu, Jia
Li, Ge
Lv, Ping
Ma, Dalong
Guo, Mingzhou
Chen, Yingyu
Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis
title Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis
title_full Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis
title_fullStr Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis
title_full_unstemmed Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis
title_short Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis
title_sort transmembrane protein 106a is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190911/
https://www.ncbi.nlm.nih.gov/pubmed/24975047
http://dx.doi.org/10.1111/jcmm.12352
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