Article

MicroRNA-183 is an oncogene targeting Dkk-3 and SMAD4 in prostate cancer

Department of Urology, San Francisco Veterans Affairs Medical Center, University of California at San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
British Journal of Cancer (Impact Factor: 4.84). 03/2013; 108(8). DOI: 10.1038/bjc.2013.125
Source: PubMed

ABSTRACT

Background:
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.

Methods:
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.

Results:
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.

Conclusion:
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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Available from: PubMed Central, Dec 17, 2014 · License: CC BY-NC-SA
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    • "。非小细胞肺癌(NSCLC)大约 占肺癌比例的85%。研究表明,在NSCLC组织和 细胞中,miR-96的表达量都高于正常的肺组织和 细胞,抑制其表达可以抑制NSCLC的增值、克隆 形成、迁移和侵袭过程。进一步研究表明,在 NSCLC中miR-96通过抑制肿瘤抑制因子RECK (reversion-inducing-cysteine-rich protein with kazal motif)的表达来起到促癌作用 [25] 。miR-182可以通 过靶向肿瘤负调控因子:细胞程序性死亡因子4 (PDCD4)起到促癌的作用 [26] 。我们研究发现,miR- 183和miR-96在肺癌细胞系和人临床肺癌组织中显 著高表达。我们进一步检测了肺癌病人临床血清 样本中miR-183家族的表达,发现其表达量也显著 升高,提示其可作为人临床肺癌检测的标志物(已 获专利申请号)。 2.3 microRNA与结肠癌 结肠癌(colorectal cancer, CRC)是最常见的恶 2 microRNA与肿瘤 2.1 microRNA与前列腺癌 前列腺癌(prostate cancer, PC)是男性中最常被 诊断出并引起死亡的恶性疾病之一,了解其发生 发展机制,并确定新的有效治疗策略至关重要。 多项研究表明,miR-183家族的三个成员,在前列 腺癌组织和细胞系中高表达,显示出潜在的促癌 功能并为前列腺癌的早期诊断提供一种可能 [12] 。 研究发现,miR-183、miR-96和miR-182在前 列腺癌组织中的表达高于正常前列腺组织,同时 它们抑制了前列腺癌细胞系中锌体内平衡。已知 锌特异性的集中于正常的前列腺组织中(比其他正 常的软组织中含量高十倍以上),锌含量的降低可 以作为前列腺癌的特征之一。实验发现miR-183家 族的三个成员正是通过抑制锌转运蛋白hZIP1(human ZRT/IRT-like protein 1)来降低锌在前列腺癌细 胞系中的含量 [13] 。 然而,该家族的成员并不是每次都同时作用。 高表达的miR-183可以促进前列腺癌细胞系的生长 和迁移能力,这个过程是通过抑制Wnt/β-catenin 信号通路中的DKK-3(Dickkopf WNT signaling pathway inhibitor 3)和SMAD4(SMAD family member 4) 来实现 [14] "

    Full-text · Article · Dec 2015
  • Source
    • "。非小细胞肺癌(NSCLC)大约 占肺癌比例的85%。研究表明,在NSCLC组织和 细胞中,miR-96的表达量都高于正常的肺组织和 细胞,抑制其表达可以抑制NSCLC的增值、克隆 形成、迁移和侵袭过程。进一步研究表明,在 NSCLC中miR-96通过抑制肿瘤抑制因子RECK (reversion-inducing-cysteine-rich protein with kazal motif)的表达来起到促癌作用 [25] 。miR-182可以通 过靶向肿瘤负调控因子:细胞程序性死亡因子4 (PDCD4)起到促癌的作用 [26] 。我们研究发现,miR- 183和miR-96在肺癌细胞系和人临床肺癌组织中显 著高表达。我们进一步检测了肺癌病人临床血清 样本中miR-183家族的表达,发现其表达量也显著 升高,提示其可作为人临床肺癌检测的标志物(已 获专利申请号)。 2.3 microRNA与结肠癌 结肠癌(colorectal cancer, CRC)是最常见的恶 2 microRNA与肿瘤 2.1 microRNA与前列腺癌 前列腺癌(prostate cancer, PC)是男性中最常被 诊断出并引起死亡的恶性疾病之一,了解其发生 发展机制,并确定新的有效治疗策略至关重要。 多项研究表明,miR-183家族的三个成员,在前列 腺癌组织和细胞系中高表达,显示出潜在的促癌 功能并为前列腺癌的早期诊断提供一种可能 [12] 。 研究发现,miR-183、miR-96和miR-182在前 列腺癌组织中的表达高于正常前列腺组织,同时 它们抑制了前列腺癌细胞系中锌体内平衡。已知 锌特异性的集中于正常的前列腺组织中(比其他正 常的软组织中含量高十倍以上),锌含量的降低可 以作为前列腺癌的特征之一。实验发现miR-183家 族的三个成员正是通过抑制锌转运蛋白hZIP1(human ZRT/IRT-like protein 1)来降低锌在前列腺癌细 胞系中的含量 [13] 。 然而,该家族的成员并不是每次都同时作用。 高表达的miR-183可以促进前列腺癌细胞系的生长 和迁移能力,这个过程是通过抑制Wnt/β-catenin 信号通路中的DKK-3(Dickkopf WNT signaling pathway inhibitor 3)和SMAD4(SMAD family member 4) 来实现 [14] "

    Full-text · Article · Jan 2015
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    • "miR-183 has previously been found to be downregulated in osteosarcoma; thus, miR-183 may be able to inhibit cell migration and invasion (24). Conversely, miR-183 has been reported to be overexpressed in prostate and colorectal cancer, stimulating tumor progression and metastasis (25,26). These results indicate that miR-183 may exert distinct functions in different tumor types. "
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