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 intestinal-type (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 treatment of
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 found 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.