MicroRNA-18a is elevated in prostate cancer and promotes tumorigenesis through suppressing STK4 in vitro and in vivo.
MicroRNA-18a is elevated in prostate cancer and promotes tumorigenesis through suppressing STK4 in vitro and in vivo.
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DOI：
10.1038/oncsis.2014.12
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发表时间：
2014-04-21
期刊：
影响因子：
6.2
通讯作者：
Lu, P-J
中科院分区：
文献类型：
--
作者：
Hsu, T-I;Hsu, C-H;Lee, K-H;Lin, J-T;Chen, C-S;Chang, K-C;Su, C-Y J.;Hsiao, M.;Lu, P-J
MicroRNAs(MiRNAs)是一类短的非编码RNA，通过转录后修饰来调节蛋白质的合成。在这项研究中，我们发现与正常对照组相比，前列腺癌标本和前列腺癌细胞系中miR-18a的表达显著上调。根据miRNAs是否调控抑癌基因或癌基因，可以将其分为两组。在我们之前的研究中，我们发现miR-18a属于miR17-92簇，在前列腺癌中上调；本研究的目的是探讨相关的调控机制。我们发现miR-18a在临床肿瘤标本和癌细胞系中表达上调。我们的生物信息学分析表明，丝氨酸/苏氨酸蛋白激酶4(STK4)3‘非翻译区包含一个与miR-18a种子区高度保守的结合部位。荧光素酶报告实验表明STK4是miR-18a的直接靶标。有趣的是，miR-18a基因敲除降低了前列腺癌细胞的生长，并通过STK4介导的AKT去磷酸化从而诱导细胞凋亡，在裸鼠体内实验中显著抑制了前列腺癌的生长。我们的结果提示miR-18a在前列腺癌中作为靶向STK4的肿瘤靶点，抑制miR-18a的表达可能为前列腺癌的治疗提供有益的选择。
MicroRNAs (miRNAs) comprise a class of short, non-coding RNAs that regulate protein synthesis through posttranscriptional modifications. In this study, we found significant upregulation of miR-18a in prostate cancer specimens and prostate cancer cell lines compared with the normal controls. MiRNAs can be separated into two groups based on whether they regulate tumor suppressors or oncogenes. In our previous study, we found that miR-18a, which belongs to the miR17-92 cluster, is upregulated in prostate cancer; the objective of this study was to investigate the associated regulatory mechanisms. We found that miR-18a is upregulated in clinical tumor specimens and cancer cell lines. Our bioinformatics analysis showed that the serine/threonine-protein kinase 4 (STK4) 3′ untranslated region contains a highly conserved binding site for the miR-18a seed region. Luciferase reporter assays were performed to indicate that STK4 is a direct target of miR-18a. Interestingly, miR-18a knockdown decreased cell growth in prostate cancer cells and significantly decreased prostate tumor growth in in vivo nude mice experiments through STK4-mediated dephosphorylation of AKT and thereby inducing apoptosis. Our results suggest that miR-18a acts as an oncomiR targeting STK4 in prostate cancer, and inhibition of miR-18a expression may offer therapeutically beneficial option for prostate cancer treatment.
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影响因子：
29.4
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1111/j.1440-1746.2008.05666.x
发表时间：
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DOI：
10.1073/pnas.0906947106
发表时间：
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影响因子：
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作者：
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通讯作者：
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