MicroRNA-212 inhibits proliferation of gastric cancer by directly repressing retinoblastoma binding protein 2.
MicroRNA-212 inhibits proliferation of gastric cancer by directly repressing retinoblastoma binding protein 2.
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DOI：
10.1002/jcb.24613
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发表时间：
2013-12-01
影响因子：
4
通讯作者：
Jihui, Jia
中科院分区：
文献类型：
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作者：
Jiping, Zeng;Ming, Fang;Jihui, Jia
视网膜母细胞瘤结合蛋白2（RBP 2）是一种新发现的组蛋白去甲基化酶，在胃癌中过表达。我们在microRNA（miRNA）水平上研究了RBP 2的上游调控机制及其在胃癌发生中的作用。我们利用生物信息学方法预测microRNA-212（miR-212）可能是RBP 2的直接上游调控因子，并在胃上皮细胞系中验证了其调控作用。过表达miR-212显著抑制RBP 2的表达水平，而敲低miR-212则促进RBP 2的表达。此外，我们通过荧光素酶测定鉴定了RBP 2 3' UTR中推定的miR-212靶向序列。MiR-212通过抑制RBP 2的表达并增加P21（CIP 1）和P27（kip 1）的表达来抑制细胞的殖民地形成能力，这两种表达在细胞周期停滞中是关键的。此外，RBP 2和miR-212在来自18名患者的肿瘤组织和匹配的正常组织中的表达进一步支持了体内结果。MiR-212直接调控胃癌中RBP 2的表达并抑制细胞生长，这可能为治疗提供新的线索。
Retinoblastoma binding protein 2 (RBP2), a newly found histone demethylase, is overexpressed in gastric cancer. We examined the upstream regulatory mechanism of RBP2 at the microRNA (miRNA) level and the role in gastric carcinogenesis. We used bioinformatics to predict that microRNA-212 (miR-212) might be a direct upstream regulator of RBP2 and verified the regulation in gastric epithelial-derived cell lines. Overexpression of miR-212 significantly inhibited the expression levels of RBP2, whereas knockdown of miR-212 promoted RBP2 expression. Furthermore, we identified the putative miR-212 targeting sequence in the RBP2 3' UTR by luciferase assay. MiR-212 inhibited the colony formation ability of cells by repressing RBP2 expression and increasing that of P21(CIP1) and P27(kip1), both critical in cell cycle arrest. In addition, the expression of RBP2 and miR-212 in tumor tissue and matched normal tissue from 18 patients further supported the results in vivo. MiR-212 directly regulates the expression of RBP2 and inhibits cell growth in gastric cancer, which may provide new clues to treatment.