Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis
Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis
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miR-23b 作为抑制癌症转移的多效调节剂的全基因组功能筛选
DOI：
10.1038/ncomms1555
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发表时间：
2011-11-01
影响因子：
16.6
通讯作者：
Xi, Jianzhong Jeff
中科院分区：
文献类型：
--
作者：
Zhang, Hanshuo;Hao, Yang;Xi, Jianzhong Jeff
miRNA对人类癌症的调控全面失调。一个关键的开放问题是有多少miRNA在功能上参与癌症的发展，特别是转移。我们系统地评估了所有已知的人类miRNAs调节某些转移相关细胞行为的能力。为了高通量筛选调控细胞迁移的miRNAs，我们开发了一种新型的自组装细胞芯片。在这里，我们发现超过20%的miRNAs在不同的细胞类型中具有迁移调节活性，表明miRNAs普遍参与迁移调节。miR-23 b在人结肠癌样品中下调，有效介导转移的多个步骤，包括体内肿瘤生长、侵袭和血管生成。它调节一组促转移靶点，包括FZD 7或MAP 3 k1。这些发现为miRNAs作为一类新的功能调节剂的生理和潜在治疗重要性提供了新的见解。
miRNA globally deregulates human carcinoma. A critical open question is how many miRNAs functionally participate in cancer development, particularly in metastasis. We systematically evaluate the capability of all known human miRNAs to regulate certain metastasis-relevant cell behaviours. To perform the high-throughput screen of miRNAs, which regulate cell migration, we developed a novel self-assembled cell microarray. Here we show that over 20% of miRNAs have migratory regulation activity in diverse cell types, indicating a general involvement of miRNAs in migratory regulation. MiR-23b, which is downregulated in human colon cancer samples, potently mediates the multiple steps of metastasis, including tumour growth, invasion and angiogenesis in vivo. It regulates a cohort of prometastatic targets, including FZD7 or MAP3k1. These findings provide new insight into the physiological and potential therapeutic importance of miRNAs as a new class of functional modulators.