microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer.
microRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer.
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DOI：
10.1038/bjc.2013.125
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发表时间：
2013-04-30
影响因子：
8.8
通讯作者：
Dahiya R
中科院分区：
文献类型：
--
作者：
Ueno K;Hirata H;Shahryari V;Deng G;Tanaka Y;Tabatabai ZL;Hinoda Y;Dahiya R
本研究的目的是基于miR微阵列鉴定前列腺癌（PC）致癌microRNA（miR），并研究这些致癌miR是否可用作PC生物标志物。首先，我们使用RWPE-1、PC-3、DU-145和LNCaP细胞进行miR微阵列和实时PCR。为了研究miR-183的功能，我们在细胞生长和伤口愈合测定中使用miR-183敲低抑制剂。我们使用了几种算法，并证实它们直接受miR-183调控。我们鉴定了三种潜在的致癌miR（miR-146 a、miR-183和miR-767- 5 P）。与RWPE-1细胞相比，PC细胞（PC-3、DU-145和LNCaP）中miR-183的表达上调。miR-183在PC组织中的表达也显著高于匹配的正常前列腺组织。此外，miR-183表达与较高的前列腺特异性抗原、较高的pT和较短的总生存期相关。在体内裸鼠实验中，miR-183敲低降低了PC细胞的细胞生长和运动性，并显著降低了前列腺肿瘤的生长。我们确定Dkk-3和SMAD 4为miR-183的潜在靶基因。我们的数据表明，致癌miR-183可能是一种新的PC生物标志物，抑制miR-183表达可能是治疗PC治疗有益的。
The purpose of this study was to identify prostate cancer (PC) oncogenic microRNAs (miRs) based on miR microarray and to investigate whether these oncogenic miRs may be useful as PC biomarkers. Initially, we carried out miR microarray and real-time PCR using RWPE-1, PC-3, DU-145 and LNCaP cells. To investigate the function of miR-183, we used a miR-183 knockdown inhibitor in cell growth and wound-healing assays. We used several algorithms and confirmed that they are directly regulated by miR-183. We identified three potential oncogenic miRs (miR-146a, miR-183 and miR-767-5P). The expression of miR-183 in PC cells (PC-3, DU-145 and LNCaP) was upregulated compared with RWPE-1 cells. MiR-183 expression was also significantly higher in PC tissues compared with that in matched normal prostate tissues. Additionally, miR-183 expression was correlated with higher prostate-specific antigen, higher pT and shorter overall survival. MiR-183 knockdown decreased cell growth and motility in PC cells and significantly decreased prostate tumour growth in in vivo nude mice experiments. We identified Dkk-3 and SMAD4 as potential target genes of miR-183. Our data suggest that oncogenic miR-183 may be useful as a new PC biomarker and that inhibition of miR-183 expression may be therapeutically beneficial as a PC treatment.
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影响因子：
3.8
作者：
Li J;Fu H;Xu C;Tie Y;Xing R;Zhu J;Qin Y;Sun Z;Zheng X
通讯作者：
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2.3
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通讯作者：
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