miR-212 is downregulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer

miR-212 is downregulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer
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DOI:
10.1002/ijc.25126
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发表时间:
2010-09-01
影响因子:
6.4
通讯作者:
Yuasa, Yasuhito
Yuasa, Yasuhito
中科院分区:
医学1区
文献类型:
--
作者:
Wada, Rie;Akiyama, Yoshimitsu;Yuasa, Yasuhito

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为了阐明微小RNA在胃癌发生中的作用,我们研究了微小RNA在胃癌(GC)细胞中的表达和功能。首先,我们使用来自3个人胃癌细胞系和非癌胃组织的总RNA进行微阵列分析。在胃癌细胞中下调的miRNAs中,miR-212在所有8种检测的胃癌细胞系中的表达均降低,并且在11例病例中的6例中也观察到miR-212在人原发性胃癌组织中的表达显著降低。前体miR-212分子的转染诱导3种GC细胞系的生长降低。使用3个不同的数据库,甲基-CpG结合蛋白MeCP 2被假定为miR-212的靶标。如在报告基因测定中所见,miR-212抑制具有MECP 2 3 '-UTR的构建体。miR-212的异位表达抑制了MeCP 2蛋白的表达,但不抑制MECP 2 mRNA水平。这些数据表明,miR-212的下调可能通过其靶基因,如MECP 2,与胃癌的发生有关。
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.