The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice.
The inhibition of the highly expressed miR-221 and miR-222 impairs the growth of prostate carcinoma xenografts in mice.
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DOI：
10.1371/journal.pone.0004029
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Ciafrè SA
中科院分区：
文献类型：
--
作者：
Mercatelli N;Coppola V;Bonci D;Miele F;Costantini A;Guadagnoli M;Bonanno E;Muto G;Frajese GV;De Maria R;Spagnoli LG;Farace MG;Ciafrè SA
miR-221和miR-222是两种高度同源的microRNA，最近在几种类型的人类肿瘤中描述了其上调，其中一些肿瘤的致癌作用通过发现其靶点p27（一种关键的细胞周期调节因子）来解释。我们先前在体外前列腺癌细胞系中显示了这种调节关系，这是miR-221/222作为增殖和致瘤性诱导剂的作用的基础。在这里，我们描述了一些体内方法，证实了我们以前的数据。miR-221的异位过表达本身能够为SCID小鼠中LNCaP衍生的肿瘤提供高生长优势。一致地，抗miR-221/222 Ekomir治疗来源于高侵袭性PC 3细胞系的已建立皮下肿瘤，天然表达高水平的miR-221/222，通过增加肿瘤内p27的量来减少肿瘤生长;这种作用是持久的，因为它在治疗后长达25天就可检测到。此外，我们提供的证据支持的临床相关性的作用，miR-221/222在前列腺癌，通过显示其在患者来源的原代细胞系中的普遍上调，我们发现一个显着的负相关性与p27的表达。这些发现表明，调节miR-221/222水平可能对前列腺癌具有治疗潜力。
MiR-221 and miR-222 are two highly homologous microRNAs whose upregulation has been recently described in several types of human tumors, for some of which their oncogenic role was explained by the discovery of their target p27, a key cell cycle regulator. We previously showed this regulatory relationship in prostate carcinoma cell lines in vitro, underlying the role of miR-221/222 as inducers of proliferation and tumorigenicity. Here we describe a number of in vivo approaches confirming our previous data. The ectopic overexpression of miR-221 is able, per se, to confer a high growth advantage to LNCaP-derived tumors in SCID mice. Consistently, the anti-miR-221/222 antagomir treatment of established subcutaneous tumors derived from the highly aggressive PC3 cell line, naturally expressing high levels of miR-221/222, reduces tumor growth by increasing intratumoral p27 amount; this effect is long lasting, as it is detectable as long as 25 days after the treatment. Furthermore, we provide evidence in favour of a clinical relevance of the role of miR-221/222 in prostate carcinoma, by showing their general upregulation in patient-derived primary cell lines, where we find a significant inverse correlation with p27 expression. These findings suggest that modulating miR-221/222 levels may have a therapeutic potential in prostate carcinoma.
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影响因子：
2.8
作者：
Prueitt, Robyn L.;Yi, Ming;Hudson, Robert S.;Wallace, Tiffany A.;Howe, Tiffany M.;Yfantis, Harris G.;Lee, Dong. H.;Stephens, Robert M.;Liu, Chang-Gong;Calin, George A.;Croce, Carlo M.;Ambs, Stefan
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Schmittgen, Thomas D.
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作者：
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通讯作者：
Chartrand, Pascal
影响因子：
29.4
作者：
Meng, Fanyin;Henson, Roger;Patel, Tushar
通讯作者：
Patel, Tushar