Transmembrane protein 106A is silenced by promoter region hypermethylation and suppresses gastric cancer growth by inducing apoptosis. Issue 8 (28th June 2014)

• Record Type: Journal Article
• Authors: Xu, Dong; Qu, Liujing; Hu, Jia; Li, Ge; Lv, Ping; Ma, Dalong; Guo, Mingzhou; Chen, Yingyu
• Is Part Of: Journal of cellular and molecular medicine. Volume 18:Issue 8(2014)
• Page Start: 1655
• Page End: 1666
• Publication Date: 2014-06-28
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12352
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12352-abs-0001"> <title>Abstract</title> <p>Inactivation of tumour suppressor genes by promoter methylation plays an important role in the initiation and progression of gastric cancer (GC). Transmembrane 106A gene (<italic>TMEM106A</italic>) encodes a novel protein of previously unknown function. This study analysed the biological functions, epigenetic changes and the clinical significance of <italic>TMEM106A</italic> in GC. Data from experiments indicate that TMEM106A is a type II membrane protein, which is localized to mitochondria and the plasma membrane. <italic>TMEM106A</italic> 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. <italic>TMEM106A</italic> 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 <italic>TMEM106A</italic> methylation in primary GCs was significantly correlated with smoking and tumour metastasis. In conclusion, <italic>TMEM106A</italic> is frequently methylated in human GC. The expression of <italic>TMEM106A</italic> is regulated by promoter hypermethylation. <italic>TMEM106A</italic> is a novel functional tumour suppressor in gastric carcinogenesis.</p> </abstract>