Up-regulation of p16 by miR-877-3p inhibits proliferation of bladder cancer.

Up-regulation of p16 by miR-877-3p inhibits proliferation of bladder cancer.
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miR-877-3p上调p16抑制膀胱癌的增殖

DOI:
10.18632/oncotarget.10575
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发表时间:
2016-08-09
期刊:
影响因子:
--
通讯作者:
Xie L
Xie L
中科院分区:
其他
文献类型:
--
作者:
Li S;Zhu Y;Liang Z;Wang X;Meng S;Xu X;Xu X;Wu J;Ji A;Hu Z;Lin Y;Chen H;Mao Y;Wang W;Zheng X;Liu B;Xie L

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尽管最近的研究表明microRNA(miRNA)通过沉默靶基因的表达来负调控基因表达,但本文报道了microRNA通过靶向特定启动子位点介导基因激活的新证据。我们在肿瘤抑制基因p16的启动子位点上鉴定了一个miR-877- 3 p结合位点,该位点在膀胱癌中经常改变。miR-877- 3 p的高表达可增加p16的表达,从而使细胞周期阻滞于G1期,抑制膀胱癌的增殖和致瘤性。进一步的证据证实,p16激活与miR-877- 3 p之间的相关性是由于直接结合。这些发现证明了miR-877- 3 p在膀胱癌细胞中的抗肿瘤功能,并揭示了miRNA参与基因调控的新模式。
Despite the recent studies which have shown that microRNA (miRNA) negatively regulates gene expression by silencing the expression of target genes, here we reported the new evidence of microRNA-mediated gene activation by targeting specific promoter sites. We identified a miR-877-3p binding site on the promoter site of tumor suppressor gene p16 which alters frequently in bladder cancer. Enforced expression of miR-877-3p could increase the expression of p16, which inhibit the proliferation and tumorigenicity of bladder cancer through cell cycle G1-phase arrest. Further evidences confirmed that the correlation between p16 activation and miR-877-3p was due to the direct binding. These findings demonstrate the anti-tumor function of miR-877-3p in bladder cancer cells and reveal a new pattern of miRNA involved gene regulation.