MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes.
MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes.
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MicroRNA-141通过靶向促膜胃基因来抑制前列腺癌干细胞和转移。
DOI：
10.1038/ncomms14270
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发表时间：
2017-01-23
影响因子：
16.6
通讯作者：
Tang DG
中科院分区：
文献类型：
--
作者：
Liu C;Liu R;Zhang D;Deng Q;Liu B;Chao HP;Rycaj K;Takata Y;Lin K;Lu Y;Zhong Y;Krolewski J;Shen J;Tang DG
microrna在调节肿瘤的发生、发展和转移中发挥重要作用。在这里，我们发现miR-200家族成员之一miR-141在异种移植和原发患者肿瘤的几种前列腺癌（PCa）干细胞/祖细胞群中表达不足。在CD44+和大块PCa细胞中强制表达miR-141可抑制肿瘤干细胞的特性，包括全克隆和球形形成以及侵袭，并抑制肿瘤再生和转移。此外，miR-141的表达增强了强上皮表型，部分丧失了间充质表型。全基因组RNA测序揭示了PCa细胞中miR-141调控的新分子靶点，包括Rho GTPase家族成员（例如CDC42、CDC42EP3、RAC1和ARPC5）和干细胞分子CD44和EZH2，它们都被证实是miR-141的直接和功能相关的靶点。我们的研究结果表明miR-141通过多种机制来阻止肿瘤的生长和转移。microrna在调节肿瘤的发生、发展和转移中具有重要作用。在这里，作者证明了miRNA141在直接靶向CD44、Rho GTPase蛋白家族成员和EZH2介导的前列腺癌干细胞中的肿瘤抑制功能。
MicroRNAs play important roles in regulating tumour development, progression and metastasis. Here we show that one of the miR-200 family members, miR-141, is under-expressed in several prostate cancer (PCa) stem/progenitor cell populations in both xenograft and primary patient tumours. Enforced expression of miR-141 in CD44+ and bulk PCa cells inhibits cancer stem cell properties including holoclone and sphere formation, as well as invasion, and suppresses tumour regeneration and metastasis. Moreover, miR-141 expression enforces a strong epithelial phenotype with a partial loss of mesenchymal phenotype. Whole-genome RNA sequencing uncovers novel miR-141-regulated molecular targets in PCa cells including the Rho GTPase family members (for example, CDC42, CDC42EP3, RAC1 and ARPC5) and stem cell molecules CD44 and EZH2, all of which are validated as direct and functionally relevant targets of miR-141. Our results suggest that miR-141 employs multiple mechanisms to obstruct tumour growth and metastasis. MicroRNAs have important roles in regulating tumor development, progression and metastasis. Here, the authors demonstrate the tumor-suppressive functions of miRNA141 in prostate cancer stem cells mediated by directly targeting CD44, Rho GTPase protein family members, and EZH2.