Epigenetic regulation of microRNA-10b and targeting of oncogenic MAPRE1 in gastric cancer

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Title
Epigenetic regulation of microRNA-10b and targeting of oncogenic MAPRE1 in gastric cancer
Author(s)
Kwoneel Kim; H C Lee; Jong Lyul ParkMirang KimSeon-Young Kim; S M Noh; K S Song; J C Kim; Yong Sung Kim
Bibliographic Citation
Epigenetics, vol. 6, no. 6, pp. 740-751
Publication Year
2011
Abstract
MicroRNAs act as negative regulators of gene expression and the altered expression of microRNAs by epigenetic mechanisms is strongly implicated in carcinogenesis. Here we report that the microRNA-10b gene (miR-10b) was silenced in gastric cancer cells by promoter methylation. In this study, using a methylation array and bisulfate pyrosequencing analysis, we found that miR-10b promoter CpGs were heavily methylated in gastric cancers. Clinicopathologic data showed that miR-10b methylation increased with patient age and occurred significantly more frequently in intestinaltype (28/44, 64%) than in diffuse-type (22/56, 39%) gastric cancers (p = 0.016). In addition, miR-10b methylation was also associated with an increase in expression of the oncogene that encodes microtubule-associated protein, RP/EB family, member 1 (MAPRE1; p = 0.004), which was identified as a potential miR-10b target. After 5-aza-2'-deoxycytidine treatmentof gastric cancer cells, miR-10b methylation was significantly decreased, and expression of miR-10b and HOXD4, which is 1 kb downstream of miR-10b, was greatly restored. Moreover, decreased MAPRE1 expression coincided with increased miR-10b expression, suggesting that miR-10b targets MAPRE1 transcription. We also f ound that transfection with precursor miR-10b into gastric cancer cells dramatically decreased MAPRE1 mRNA and protein, resulting in a significant decrease in colony formation and cell growth rates. Thus, we show a tumor-suppressive role for miR-10b in gastric carcinogenesis. miR-10b methylation may be a useful molecular biomarker for assessing the risk of gastric cancer development, and modulation of miR-10b may represent a therapeutic approach for treating gastric cancer.
Keyword
CpG methylationGastric cancerHOXD4MAPRE1miR-10b
ISSN
1559-2294
Publisher
T&F (Taylor & Francis)
DOI
http://dx.doi.org/10.4161/epi.6.6.15874
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Korea Bioinformation Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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