Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p): Inhibition of bladder cancer cell aggressiveness.
Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p): Inhibition of bladder cancer cell aggressiveness.
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DOI：
10.18632/oncotarget.8668
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发表时间：
2016-05-10
期刊：
影响因子：
--
通讯作者：
Seki N
中科院分区：
文献类型：
--
作者：
Matsushita R;Yoshino H;Enokida H;Goto Y;Miyamoto K;Yonemori M;Inoguchi S;Nakagawa M;Seki N
在microRNA(MiRNA)的生物发生过程中，miRNA的引导链整合到RNA诱导的沉默复合体(RISC)中，而乘客链通过降解而失活。对我们的膀胱癌miRNA表达特征进行的深度测序分析表明，microRNA(MiR)-145-5p(引导链)和miR-145-3p(客体链)在膀胱癌组织中显著下调。众所周知，miR-145-5p在多种类型的癌症中发挥肿瘤抑制作用。然而，miR-145-3p对癌细胞的影响仍不明确。本研究旨在探讨miR-145-5p/miR-145-3p调控的miR-145-3p和BC致癌途径及靶点的功能意义。在BC细胞中异位表达miR-145-5p或miR-145-3p显著抑制癌细胞的生长、迁移和侵袭，并诱导细胞凋亡。编码具有PHD和环指结构域1的泛素样蛋白的基因(Uhrf1)是这些miRNAs的直接靶标。沉默uhrf1可诱导BC细胞凋亡，抑制癌细胞的增殖、迁移和侵袭。此外，bc临床标本中存在uhrf1的高表达，uhrf1高表达组的病因特异性生存率明显低于低表达组。综上所述，我们目前的数据表明miR-145的两条链(miR-145-5p：引导链和miR-145-3p：客体链)通过调节uhrf1在BC细胞中发挥关键作用。肿瘤抑制miRNAs分子靶点的确定为深入了解BC致癌的潜在机制提供了新的见解，并提出了新的治疗策略。
In microRNA (miRNA) biogenesis, the guide-strand of miRNA integrates into the RNA induced silencing complex (RISC), whereas the passenger-strand is inactivated through degradation. Analysis of our miRNA expression signature of bladder cancer (BC) by deep-sequencing revealed that microRNA (miR)-145-5p (guide-strand) and miR-145-3p (passenger-strand) were significantly downregulated in BC tissues. It is well known that miR-145-5p functions as a tumor suppressor in several types of cancer. However, the impact of miR-145-3p on cancer cells is still ambiguous. The aim of the present study was to investigate the functional significance of miR-145-3p and BC oncogenic pathways and targets regulated by miR-145-5p/miR-145-3p. Ectopic expression of either miR-145-5p or miR-145-3p in BC cells significantly suppressed cancer cell growth, migration and invasion and it also induced apoptosis. The gene encoding ubiquitin-like with PHD and ring finger domains 1 (UHRF1) was a direct target of these miRNAs. Silencing of UHRF1 induced apoptosis and inhibited cancer cell proliferation, migration, and invasion in BC cells. In addition, overexpressed UHRF1 was confirmed in BC clinical specimens, and the high UHRF1 expression group showed a significantly poorer cause specific survival rate in comparison with the low expression group. Taken together, our present data demonstrated that both strands of miR-145 (miR-145-5p: guide-strand and miR-145-3p: passenger-strand) play pivotal roles in BC cells by regulating UHRF1. The identification of the molecular target of a tumor suppressive miRNAs provides novel insights into the potential mechanisms of BC oncogenesis and suggests novel therapeutic strategies.
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耐法前列腺癌的microRNA表达特征：microRNA-221/222簇作为肿瘤抑制剂和疾病进展标记物的作用。
影响因子：
8.8
作者：
Goto Y;Kojima S;Nishikawa R;Kurozumi A;Kato M;Enokida H;Matsushita R;Yamazaki K;Ishida Y;Nakagawa M;Naya Y;Ichikawa T;Seki N
通讯作者：
Seki N
影响因子：
13.6
作者：
Di Leva G;Croce CM
通讯作者：
Croce CM
影响因子：
8.8
作者：
Matsushita R;Seki N;Chiyomaru T;Inoguchi S;Ishihara T;Goto Y;Nishikawa R;Mataki H;Tatarano S;Itesako T;Nakagawa M;Enokida H
通讯作者：
Enokida H
影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R
DOI：
10.1073/pnas.0808042106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Sachdeva, Mohit;Zhu, Shoumin;Mo, Yin-Yuan
通讯作者：
Mo, Yin-Yuan