Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Int J Cancer. 2010 Sep 1;127(5):1106-14. doi: 10.1002/ijc.25126.
To clarify the role of micro (mi) RNAs in gastric carcinogenesis, we studied the expression and function of miRNAs in gastric carcinoma (GC) cells. Initially, we performed microarray analysis using total RNA from 3 human GC cell lines and noncancerous gastric tissue. Among the downregulated miRNAs in GC cells, miR-212 expression was decreased in all 8 GC cell lines examined and a significant decrease of miR-212 expression in human primary GC tissues was also observed in 6 of 11 cases. Transfection of the precursor miR-212 molecule induced decreased growth of 3 GC cell lines. Using 3 different databases, methyl-CpG-binding protein MeCP2 was postulated to be a target of miR-212. As seen on reporter assaying, miR-212 repressed the construct with the MECP2 3'-UTR. Ectopic expression of miR-212 repressed expression of the MeCP2 protein but not the MECP2 mRNA level. These data suggest that downregulation of miR-212 may be related to gastric carcinogenesis through its target genes, such as MECP2.
为了阐明 micro (mi)RNAs 在胃癌发生中的作用,我们研究了 miRNA 在胃癌(GC)细胞中的表达和功能。最初,我们使用来自 3 个人类 GC 细胞系和非癌性胃组织的总 RNA 进行了微阵列分析。在 GC 细胞中下调的 miRNAs 中,miR-212 在所有 8 个 GC 细胞系中均降低,并且在 11 例人原发性 GC 组织中也观察到 miR-212 的表达显著降低。miR-212 前体分子的转染诱导 3 个 GC 细胞系的生长减少。使用 3 个不同的数据库,推测甲基-CpG 结合蛋白 MeCP2 是 miR-212 的靶标。如报告测定所见,miR-212 抑制了具有 MECP2 3'-UTR 的构建体。miR-212 的异位表达抑制了 MeCP2 蛋白的表达,但不抑制 MECP2 mRNA 水平。这些数据表明,miR-212 的下调可能通过其靶基因(如 MECP2)与胃癌发生有关。