Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, United States of America.
PLoS One. 2013;8(1):e55502. doi: 10.1371/journal.pone.0055502. Epub 2013 Jan 30.
Recently miR-182 has been reported to be over-expressed in prostate cancer (PC) tissues, however detailed functional analysis of miR-182-5p has not been carried out. The purpose of this study was to: 1. analyze the function of miR-182-5p in prostate cancer, 2. assess its usefulness as a tumor marker, 3. identify miR-182-5p target genes in PC, 4. investigate the potential for miR-182-5p inhibitor to be used in PC treatment. Initially we found that miR-182-5p expression was significantly higher in prostate cancer tissues and cell lines compared to normal prostate tissues and cells. Moreover high miR-182-5p expression was associated with shorter overall survival in PC patients. To study the functional significance of miR-182-5p, we knocked down miR-182-5p with miR-182-5p inhibitor. After miR-182-5p knock-down, prostate cancer cell proliferation, migration and invasion were decreased. We identified FOXF2, RECK and MTSS1 as potential target genes of miR-182-5p using several algorithms which was confirmed by 3'UTR luciferase assay and Western analysis. Knock-down of miR-182-5p also significantly decreased in vivo prostate tumor growth. In conclusion this is the first report documenting that over-expression of miR-182-5p is associated with prostate cancer progression and potentially useful as a prognostic biomarker. Also knock down of miR-182-5p in order to increase expression of tumor suppressor genes FOXF2, RECK and MTSS1 may be of therapeutic benefit in prostate cancer treatment.
最近有研究报道 miR-182 在前列腺癌(PC)组织中过表达,然而 miR-182-5p 的详细功能分析尚未进行。本研究旨在:1. 分析 miR-182-5p 在前列腺癌中的功能,2. 评估其作为肿瘤标志物的有用性,3. 鉴定 PC 中 miR-182-5p 的靶基因,4. 研究 miR-182-5p 抑制剂在 PC 治疗中的应用潜力。最初我们发现,miR-182-5p 在前列腺癌组织和细胞系中的表达明显高于正常前列腺组织和细胞。此外,miR-182-5p 高表达与 PC 患者总生存时间缩短相关。为了研究 miR-182-5p 的功能意义,我们用 miR-182-5p 抑制剂敲低 miR-182-5p。miR-182-5p 敲低后,前列腺癌细胞增殖、迁移和侵袭能力降低。我们使用几种算法鉴定了 FOXF2、RECK 和 MTSS1 作为 miR-182-5p 的潜在靶基因,这通过 3'UTR 荧光素酶检测和 Western 分析得到了证实。miR-182-5p 的敲低也显著降低了体内前列腺肿瘤的生长。总之,这是首次报道 miR-182-5p 的过表达与前列腺癌进展相关,并可能作为一种预后生物标志物有用。此外,敲低 miR-182-5p 以增加肿瘤抑制基因 FOXF2、RECK 和 MTSS1 的表达可能对前列腺癌治疗具有治疗益处。