Identification of miR-30d as a novel prognostic maker of prostate cancer.
Identification of miR-30d as a novel prognostic maker of prostate cancer.
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DOI：
10.18632/oncotarget.696
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发表时间：
2012-11
期刊：
影响因子：
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通讯作者：
Ishiguro H
中科院分区：
文献类型：
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作者：
Kobayashi N;Uemura H;Nagahama K;Okudela K;Furuya M;Ino Y;Ito Y;Hirano H;Inayama Y;Aoki I;Nagashima Y;Kubota Y;Ishiguro H
前列腺癌（PCa）是西方国家男性中最常见的恶性肿瘤。microRNA（miRNA）具有作为生物标志物和治疗靶点用于治疗各种癌症的潜力。我们使用miRNA微阵列和qPCR发现miR-30 d在3种PCa细胞系（PC 3、DU 145和LNCaP）中的表达显著高于2种正常前列腺细胞系（RWPE-1和PrSc）。临床病理研究显示，胃癌组织中miR-30 d的表达水平显著高于配对的正常对照组（P = 0.03）。此外，miR-30 d −高组的生化复发时间较短（P = 0.026）。miR-30 d过表达促进PCa细胞的体外增殖和侵袭。miR-30 d耗尽的PCa细胞的接种在体内显著减少肿瘤体积。利用报告基因分析，我们鉴定了miR-30 d作为SOCS 1表达的下调因子，其通过直接结合SOCS 1的3 '-UTR。miR-30 d通过下调SOCS 1的表达来调节磷酸化STAT 3、MMP-2和MMP-9的表达。SOCS 1 mRNA和蛋白在前列腺癌组织中的表达均显著下调。miR-30 d表达与SOCS 1表达呈负相关（P = 0.03）。miR-30 d −高/SOCS 1 −低组与早期生化复发风险增加相关（P = 0.0057）。总之，miR-30 d似乎是PCa进展的一种新的独立预后标志物，使临床医生能够识别需要更强化治疗的患者。
Prostate cancer (PCa) is the most common malignant carcinoma that develops in men in Western countries. MicroRNA (miRNA) have the potential to be used as biomarkers and therapeutic targets for the treatment of various cancers. We found significantly higher expression of miR-30d in 3 PCa cell lines (PC3, DU145 and LNCaP) compared with 2 normal prostate cell lines (RWPE-1 and PrSc) using miRNA microarrays and qPCR. Clinicopathological study revealed that miR-30d expression levels were significantly higher in cancer tissue samples than in the paired normal controls (P = 0.03). Furthermore, the miR-30d−high group had shorter time to biochemical recurrence (P = 0.026). MiR-30d overexpressed PCa cells promoted proliferation and invasion in vitro. Inoculation of miR-30d depleted PCa cells dramatically reduced tumor volumes in vivo. Using reporter gene assay, we identified miR-30d as a downregulator of SOCS1 expression by directly binding to 3'-UTR of SOCS1. MiR-30d regulated the expression of phospho-STAT3, MMP-2 and MMP-9 through the downregulation of SOCS1. The levels of SOCS1 mRNA and protein were significantly down-regulated in prostate cancer tissues. Consistently, miR-30d expression was inversely correlated with SOCS1 expression (P = 0.03). The miR-30d−high/SOCS1−low group was associated with an increased risk of early biochemical recurrence (P = 0.0057). Taken together, miR-30d appears to be a novel independent prognostic marker of PCa progression that allows clinicians to identify patients who need more intensive treatments.