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学科主题基础医学
Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis
Xu, Dong1,2; Qu, Liujing1,2; Hu, Jia1,2; Li, Ge1,2; Lv, Ping1,2; Ma, Dalong1,2; Guo, Mingzhou3; Chen, Yingyu1,2
关键词transmembrane protein 106A gastric cancer apoptosis epigenetic alteration
刊名JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
2014-08-01
DOI10.1111/jcmm.12352
18期:8页:1655-1666
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology ; Medicine, Research & Experimental
研究领域[WOS]Cell Biology ; Research & Experimental Medicine
关键词[WOS]FRONTOTEMPORAL LOBAR DEGENERATION ; CPG ISLAND METHYLATION ; RISK-FACTOR ; TMEM106B ; GENES ; EXPRESSION ; CASPASE-2 ; PREDICTOR ; PROGNOSIS ; CARCINOMA
英文摘要

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.

语种英语
WOS记录号WOS:000341712600015
项目编号973-2011CB910103 ; 2010CB912802 ; 863-2012AA02A203 ; 2012AA02A504
资助机构National Key Basic Research Program of China ; National High Technology Research and Development Program of China
引用统计
被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65443
专题北京大学基础医学院_免疫学系
北京大学基础医学院
北京大学口腔医学院_儿童口腔科
作者单位1.Peking Univ, Hlth Sci Ctr, Minist Hlth, Key Lab Med Immunol, Beijing 100191, Peoples R China
2.Peking Univ, Ctr Human Dis Genom, Beijing 100191, Peoples R China
3.Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing, Peoples R China
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Xu, Dong,Qu, Liujing,Hu, Jia,et al. Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2014,18(8):1655-1666.
APA Xu, Dong.,Qu, Liujing.,Hu, Jia.,Li, Ge.,Lv, Ping.,...&Chen, Yingyu.(2014).Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,18(8),1655-1666.
MLA Xu, Dong,et al."Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 18.8(2014):1655-1666.
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