MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells
MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells
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DOI：
10.1016/j.bbrc.2009.03.077
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发表时间：
2009-06-05
影响因子：
3.1
通讯作者：
Huang, Yiran
中科院分区：
文献类型：
--
作者：
Li, Tao;Li, Dong;Huang, Yiran
前列腺癌是男性最常见的恶性肿瘤之一。最近的研究表明，microRNA-21 (miR-21) 在包括前列腺癌在内的多种类型的癌症中过度表达。对胶质瘤、结肠癌细胞、肝细胞癌细胞和乳腺癌细胞的研究表明，miR-21参与肿瘤的生长、侵袭和转移。然而，人们对 miR-21 在前列腺癌中的作用知之甚少。在这项研究中，检测了 miR-21 对前列腺癌细胞增殖、凋亡和侵袭的影响。此外，通过报道的基于 RISC 免疫共沉淀的生化方法鉴定了 miR-21 的靶标。在雄激素非依赖性前列腺癌细胞系 DU145 和 PC-3 中，反义寡核苷酸灭活 miR-21 导致对细胞凋亡敏感并抑制细胞运动和侵袭，而细胞增殖不受影响。我们确定了肉豆蔻酰化富含丙氨酸的蛋白激酶 C 底物 (MARCKS)，它在细胞运动中发挥着关键作用，是前列腺癌细胞的新靶点。我们的数据表明，miR-21 可以促进前列腺癌细胞的凋亡抵抗、运动和侵袭，而 miR-21 的这些作用可能部分归因于其对 PDCD4、TPM1 和 MARCKS 的调节。因此，使用 miR-21 抑制策略的基因治疗可能可用作前列腺癌治疗。 (C) 2009 Elsevier Inc. 保留所有权利。
Prostate cancer is one of the most common malignant cancers in men. Recent studies have shown that microRNA-21 (miR-21) is overexpressed in various types of cancers including prostate cancer. Studies on glioma, colon cancer cells, hepatocellular cancer cells and breast cancer cells have indicated that miR-21 is involved in tumor growth, invasion and metastasis. However, the roles of miR-21 in prostate cancer are poorly understood. In this study, the effects of miR-21 on prostate cancer cell proliferation, apoptosis, and invasion were examined. In addition, the targets of miR-21 were identified by a reported RISC-coimmunoprecipitation-based biochemical method. Inactivation of miR-21 by antisense oligonucleotides in androgen-independent prostate cancer cell lines DU145 and PC-3 resulted in sensitivity to apoptosis and inhibition of cell motility and invasion, whereas cell proliferation were not affected. We identified myristoylated alanine-rich protein kinase c substrate (MARCKS), which plays key roles in cell motility, as a new target in prostate cancer cells. Our data suggested that miR-21 could promote apoptosis resistance, motility, and invasion in prostate cancer cells and these effects of miR-21 may be partly due to its regulation of PDCD4, TPM1, and MARCKS. Gene therapy using miR-21 inhibition strategy may therefore be useful as a prostate cancer therapy. (C) 2009 Elsevier Inc. All rights reserved.