Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer
Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer
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DOI：
10.1038/jhg.2012.95
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发表时间：
2012-11-01
影响因子：
3.5
通讯作者：
Seki, Naohiko
中科院分区：
文献类型：
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作者：
Fuse, Miki;Kojima, Satoko;Seki, Naohiko
microRNAs（miRNAs）在人类肿瘤的发生、发展和转移中起着关键作用。miRNA在许多人类癌症中异常表达，并且可以作为靶向许多癌症相关基因的肿瘤抑制因子或癌基因发挥作用。本研究旨在确定前列腺癌（PCa）中新的miRNA调控分子通路。PCa临床标本中的miRNA表达特征显示，与非PCa组织相比，56种miRNA在PCa中显著下调。我们集中于前四个下调的miRNA（miR-187、miR-205、miR-222和miR-31）来研究它们在PCa细胞中的功能意义。在PCa标本（15个PCa组织和17个非PCa组织）中验证了这四种miRNA的表达水平，以确认它们在这些PCa组织中显着降低。功能获得性分析表明，miR-222和miR-31抑制PCa细胞系（PC 3和DU 145）的细胞增殖、侵袭和迁移，表明miR-222和miR-31可能在PCa中起肿瘤抑制剂的作用。使用miR-222或miR-31转染子进行全基因组基因表达分析以确定它们影响的途径，结果表明许多癌症相关基因在PC 3细胞中受到这些miRNA的调控。识别和分类肿瘤抑制性miRNAs调控的分子通路可以为PCa肿瘤发生的分子机制提供新的信息。Journal of Human Genetics（2012）57，691-699; doi：10.1038/jhg.2012.95; 2012年8月2日在线发表
microRNAs (miRNAs) have key roles in human tumorigenesis, tumor progression and metastasis. miRNAs are aberrantly expressed in many human cancers and can function as tumor suppressors or oncogenes that target many cancer-related genes. This study seeks to identify novel miRNA-regulated molecular pathways in prostate cancer (PCa). The miRNA expression signature in clinical specimens of PCa showed that 56 miRNAs were significantly downregulated in PCa compared with non-PCa tissues. We focused on the top four downregulated miRNAs (miR-187, miR-205, miR-222 and miR-31) to investigate their functional significance in PCa cells. Expression levels of these four miRNAs were validated in PCa specimens (15 PCa tissues and 17 non-PCa tissues) to confirm that they were significantly reduced in these PCa tissues. Gain-of-function analysis demonstrated that miR-222 and miR-31 inhibited cell proliferation, invasion and migration in PCa cell lines (PC3 and DU145), suggesting that miR-222 and miR-31 may act as tumor suppressors in PCa. Genome-wide gene expression analysis using miR-222 or miR-31 transfectants to identify the pathways they affect showed that many cancer-related genes are regulated by these miRNAs in PC3 cells. Identification and categorization of the molecular pathways regulated by tumor suppressive miRNAs could provide new information about the molecular mechanisms of PCa tumorigenesis. Journal of Human Genetics (2012) 57, 691-699; doi:10.1038/jhg.2012.95; published online 2 August 2012