Down-regulation of Dicer and Ago2 is associated with cell proliferation and apoptosis in prostate cancer
Down-regulation of Dicer and Ago2 is associated with cell proliferation and apoptosis in prostate cancer
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DOI：
10.1007/s13277-014-2462-3
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发表时间：
2014-11-01
期刊：
影响因子：
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通讯作者：
Ye, Ding-Wei
中科院分区：
文献类型：
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作者：
Bian, Xiao-Jie;Zhang, Gui-Ming;Ye, Ding-Wei
Dicer和Argonaute 2（Ago 2）是不仅负责RNA干扰而且还负责microRNA合成的关键组分。本研究探讨Dicer和Ago 2在前列腺癌（Pca）中的作用。首先，通过免疫组织化学（IHC）检测Pca组织中Dicer和Ago 2的表达水平，并与病理特征进行比较。然后，利用RNA干扰技术下调Pca细胞系LNCaP、PC-3和DU 145中Dicer和Ago 2的表达水平，并分别采用CCK-8法和流式细胞术检测其对细胞增殖、凋亡和细胞周期的影响。我们发现，Pca组织中的Dicer和Ago 2表达水平高于邻近良性组织，并与较低的Gleason模式相关，局部Pca中的Dicer表达除外。在体外，沉默Dicer或Ago 2抑制LNCaP、PC-3和DU 145中的细胞增殖并诱导凋亡，以及在雄激素依赖性LNCaP中将细胞周期阻滞在G2/M期，或在雄激素非依赖性PC-3和DU 145中将细胞周期阻滞在S期。总而言之，这些发现表明Dicer和Ago 2在Pca的增殖、细胞凋亡和细胞周期中发挥重要作用，并且可能既是Pca进展的有希望的生物标志物，也是潜在的治疗靶点。
Dicer and Argonaute2 (Ago2) are critical components responsible not only for RNA interference but also for microRNA synthesis. The present study investigated the roles of Dicer and Ago2 in prostate cancer (Pca). First, the expression levels of Dicer and Ago2 in Pca tissues were determined by immunohistochemistry (IHC) and compared with pathological features. Next, RNA interference was used to down-regulate the expression levels of Dicer and Ago2 in the Pca cell lines LNCaP, PC-3, and DU145, and effects on proliferation, apoptosis, and cell cycle were detected using the CCK-8 assay and flow cytometry, respectively. We found that Dicer and Ago2 expression levels in Pca tissues were higher than those in adjacent benign tissues and correlated with lower Gleason patterns, with the exception of Dicer expression in localized Pca. In vitro, silencing Dicer or Ago2 inhibited cell proliferation and induced apoptosis in LNCaP, PC-3, and DU145, as well as arrested the cell cycle at the G2/M phase in androgen-dependent LNCaP, or at S phase in the androgen-independent PC-3 and DU145. Altogether these findings suggest that Dicer and Ago2 play important roles in proliferation, apoptosis, and the cell cycle in Pca and might serve as both promising biomarkers for Pca progression and potential therapeutic targets.