A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer
A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer
复制标题
一种新型长非编码 RNA AK001796 作为癌基因，参与白藜芦醇对肺癌细胞生长的抑制。
DOI：
10.1016/j.taap.2015.04.003
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发表时间：
2015-06-01
影响因子：
3.8
通讯作者：
Jiang, Yiguo
中科院分区：
文献类型：
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作者：
Yang, Qiaoyuan;Xu, Enwu;Jiang, Yiguo
肺癌是世界上最常见的癌症。白藜芦醇对长链非编码RNA（lncRNA）的特异性靶向作用为癌症的化学预防开辟了新的途径。在本研究中，我们通过微阵列分析发现，25 μ mol/L白藜芦醇处理肺癌A549细胞后，21个lncRNA表达上调，19个lncRNA表达下调。AK 001796是表达变化最明显的lncRNA，在肺癌组织和细胞系中过表达，但在白藜芦醇处理的肺癌细胞中表达下调。通过监测体外细胞增殖和生长以及体内肿瘤生长，我们观察到在AK 001796敲低后肺癌细胞中细胞活力的显著降低和肿瘤发生的缓慢生长。我们还发现，AK 001796敲低导致细胞周期停滞，肺癌细胞中G（0）/G（1）细胞的百分比显著增加。通过使用细胞周期途径特异性PCR阵列，我们检测了与lncRNA AK 001796敲低相关的许多细胞周期相关基因的变化。我们进一步研究了AK 001796是否参与白藜芦醇的抗癌作用，结果表明，降低lncRNA AK 001796水平可能会削弱白藜芦醇对细胞增殖的抑制作用。据我们所知，这是第一个研究报告白藜芦醇诱导肺癌lncRNA表达谱的变化。(C)2015 Elsevier Inc. All rights reserved.
Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 mu mol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G(0)/G(1) in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer. (C) 2015 Elsevier Inc. All rights reserved.