miR-24 regulates CDKN1B/p27 expression in prostate cancer
miR-24 regulates CDKN1B/p27 expression in prostate cancer
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DOI：
10.1002/pros.23156
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发表时间：
2016-05-15
期刊：
影响因子：
2.8
通讯作者：
McKenna, Declan J.
中科院分区：
文献类型：
--
作者：
Lynch, Seodhna M.;McKenna, Michael M.;McKenna, Declan J.
背景微小RNA（miRNA）是小的非编码RNA分子，在癌症中具有重要作用。在前列腺癌中，一些 miRNA 表达异常，表明它们可能是该疾病的诊断、预后和潜在治疗干预的有用标记。然而，单个 miRNA 对这种疾病的发生和进展的贡献仍然知之甚少。本研究调查了 miR-24 的作用，而 miR-24 与前列腺癌的关系尚未得到广泛研究。方法我们使用 PCR 来研究 miR-24 在一组前列腺癌细胞系和一系列临床前列腺活检标本中的表达。通过一系列体外生物测定评估了前列腺癌细胞中 miR-24 表达的生物学意义，并研究了对拟议靶标 p27 (CDKN1B) 和 p16 (CDK2NA) 的影响。 结果我们表明，与正常前列腺上皮细胞系相比，前列腺癌细胞系中 miR-24 表达显着降低。相对于匹配的正常组织，在针芯和前列腺切除肿瘤组织中也更频繁地观察到 miR-24 表达的降低。低 miR-24 表达与高 PSA 血清水平和前列腺癌进展增加的其他标志物相关。重要的是，miR-24 的过度表达抑制前列腺癌细胞的细胞周期、增殖、迁移和克隆形成潜力，并诱导细胞凋亡。 p27 和 p16 被证实是前列腺癌细胞中 miR-24 的靶标，并且在临床前列腺切除标本中揭示了 miR-24 和 p27 之间的显着负相关。结论这些发现提供了证据，表明 miR-24 在前列腺癌中具有肿瘤抑制作用，并且还靶向前列腺癌细胞中的 p27 和 p16。我们认为它可能是一种有用的进展生物标志物或该疾病治疗干预的焦点。前列腺 76:637-648, 2016。(c) 2016 Wiley periodicals, Inc.
BACKGROUNDMicroRNAs (miRNAs) are small, non-coding RNA molecules with an important role in cancer. In prostate cancer, several miRNAs are expressed abnormally suggesting they may be useful markers for diagnosis, prognosis, and potential therapeutic intervention in this disease. However, the contribution of individual miRNAs to the development and progression of this disease remains poorly understood. This study investigated the role of miR-24, which has not been extensively studied in relation to prostate cancer.METHODSWe used PCR to investigate the expression of miR-24 in a panel of prostate cancer cell-lines and in a series of clinical prostate biopsy specimens. The biological significance of miR-24 expression in prostate cancer cells was assessed by a series of in vitro bioassays and the effect on proposed targets p27 (CDKN1B) and p16 (CDK2NA) was investigated.RESULTSWe showed that miR-24 expression was significantly lower in prostate cancer cell lines compared to a normal prostate epithelial cell line. Decreased expression of miR-24 was also more frequently observed in both needle core and prostatectomy tumor tissue relative to matched normal tissue. Low miR-24 expression correlated with high PSA serum levels and other markers of increased prostate cancer progression. Importantly, over-expression of miR-24 inhibited cell cycle, proliferation, migration, and clonogenic potential of prostate cancer cells, as well as inducing apoptosis. p27 and p16 were confirmed as targets of miR-24 in prostate cancer cells and a significant inverse correlation between miR-24 and p27 was revealed in clinical prostatectomy specimens.CONCLUSIONSThese findings provide evidence that miR-24 has a tumor suppressor role in prostate cancer and also targets p27 and p16 in prostate cancer cells. We propose that it may be a useful progression biomarker or focus of therapeutic intervention for this disease. Prostate 76:637-648, 2016. (c) 2016 Wiley Periodicals, Inc.