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- Epigenetic regulation of microRNA-10b and targeting of oncogenic MAPRE1 in gastric cancer
- Kwoneel Kim; H C Lee; Jong Lyul Park; Mirang Kim; Seon-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
- 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.
- CpG methylation; Gastric cancer; HOXD4; MAPRE1; miR-10b
- T&F (Taylor & Francis)
- 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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