Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer.
Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer.
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DOI：
10.1038/bjc.2011.462
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发表时间：
2012-01-17
影响因子：
8.8
通讯作者：
Seki, N.
中科院分区：
文献类型：
--
作者：
Kojima, S.;Chiyomaru, T.;Kawakami, K.;Yoshino, H.;Enokida, H.;Nohata, N.;Fuse, M.;Ichikawa, T.;Naya, Y.;Nakagawa, M.;Seki, N.
关键词：
我们最近对miRNA表达特征的分析表明，miR-1和miR-133a在几种类型的癌症中显着降低。有趣的是，miR-1和miR-133a位于人类基因组的同一染色体位点上。我们检测了miR-1和miR-133a在前列腺癌（PCa）细胞中的功能意义，并鉴定了miR-1和miR-133a调节的新分子靶点。与非PCa组织相比，PCa组织中miR-1和miR-133a的表达水平明显下调。在PC3和DU145细胞中恢复miR-1或miR-133a显示出明显的增殖、迁移和侵袭抑制。通过全基因组基因表达分析和荧光素酶报告基因测定鉴定分子靶标，发现嘌呤核苷磷酸化酶（PNP）受这两个mirna的直接调控。PNP基因的沉默抑制了PC3和DU145细胞的增殖、迁移和侵袭。免疫组化检测PCa标本中PNP阳性染色。miR-1和miR-133a的下调是PCa中常见的事件，两者都具有肿瘤抑制作用。PNP是两种mirna的新靶基因，并可能具有致癌基因的功能。因此，鉴定由mirna调控的新型分子网络可能为PCa癌变的潜在原因提供新的见解。
Our recent analyses of miRNA expression signatures showed that miR-1 and miR-133a were significantly reduced in several types of cancer. Interestingly, miR-1 and miR-133a are located on the same chromosomal locus in the human genome. We examined the functional significance of miR-1 and miR-133a in prostate cancer (PCa) cells and identified the novel molecular targets regulated by both miR-1 and miR-133a. The expression levels of miR-1 and miR-133a were significantly downregulated in PCa compared with non-PCa tissues. Restoration of miR-1 or miR-133a in PC3 and DU145 cells revealed significant inhibition of proliferation, migration, and invasion. Molecular target identification by genome-wide gene expression analysis and luciferase reporter assay showed that purine nucleoside phosphorylase (PNP) was directly regulated by both miRNAs. Silencing of the PNP gene inhibited proliferation, migration, and invasion in both PC3 and DU145 cells. Immunohistochemistry detected positive staining of PNP in PCa specimens. Downregulation of miR-1 and miR-133a was a frequent event in PCa and both function as tumour suppressors. The PNP is a novel target gene of both miRNAs and potentially functions as an oncogene. Therefore, identification of novel molecular networks regulated by miRNAs may provide new insights into the underlying causes of PCa oncogenesis.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
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作者：
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作者：
Arpaia, E;Benveniste, P;Di Cristofano, A;Gu, Y;Dalal, I;Kelly, S;Hershfield, M;Pandolfi, P P;Roifman, C M;Cohen, A
通讯作者：
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作者：
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通讯作者：
Ravandi, Farhad