Strong reduction of AGO2 expression in melanoma and cellular consequences.
Strong reduction of AGO2 expression in melanoma and cellular consequences.
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DOI：
10.1038/bjc.2013.646
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发表时间：
2013-12-10
影响因子：
8.8
通讯作者：
Bosserhoff, A-K
中科院分区：
文献类型：
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作者：
Voeller, D.;Reinders, J.;Meister, G.;Bosserhoff, A-K
microRNA（miRNAs）的加工是一个高度受控的过程。在几种类型的癌症中观察到了miRNA表达的失调，但直到今天才分析了miRNA加工酶的变化。在这项研究中，我们分析了Argonaute 2（AGO 2，EIF 2C 2），作为miRNA加工组合的一个主要因素，在癌症发展的背景下，特别是在黑色素瘤中。我们用生物化学方法（qRT-PCR、蛋白质印迹和免疫荧光研究）确定了黑色素瘤以及其他癌症中的AGO 2表达水平，并在迁移测定中分析了细胞行为。特别是在黑色素瘤中，我们发现AGO 2的表达与原代黑色素细胞相比明显减少。AGO 2表达的降低仅在蛋白水平上，而mRNA水平保持不变，暗示转录后调节。我们可以证明，由于小干扰RNA和短发夹RNA的功能增加，AGO 2在黑色素瘤中的重新表达导致调节作用的强烈改善。我们确定了黑色素瘤特异性AGO 2下调和相应的RNAi效率降低。这些发现将有助于了解恶性黑色素瘤的分子基础，并可能导致治疗策略的改进。
Processing of microRNAs (miRNAs) is a highly controlled process. Deregulation of miRNA expression was observed in several types of cancer but changes in the miRNA-processing enzymes have not been analysed until today. In this study, we analysed Argonaute2 (AGO2, EIF2C2), as one main factor of the miRNA processing ensemble, in the context of cancer development, especially in melanoma. We determined the AGO2 expression level in melanoma, as well as in other cancers, with biochemical approaches (qRT–PCR, western blot and immunofluorescence studies) and analysed the cell behaviour in migration assays. Specifically in melanoma, we revealed a strong reduction of AGO2 expression compared with primary melanocytes. The reduction of AGO2 expression was only found on protein level, whereas the mRNA level stayed unchanged hinting to post-transcriptional regulation. We could show that re-expression of AGO2 in melanoma leads to a strong improvement of regulatory effects due to increased functionality of small-interfering RNAs and short hairpin RNAs. We identified melanoma-specific downregulation of AGO2 and corresponding reduced RNAi efficiency. These findings will help to understand the molecular basis of malignant melanoma and can potentially lead to an improvement of therapeutic strategies.
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影响因子：
6.5
作者：
Luo, Chonglin;Tetteh, Paul W.;Eichmueller, Stefan B.
通讯作者：
Eichmueller, Stefan B.
影响因子：
9.2
作者：
Deng Y;Deng H;Bi F;Liu J;Bemis LT;Norris D;Wang XJ;Zhang Q
通讯作者：
Zhang Q
影响因子：
3.7
作者：
Ma Z;Swede H;Cassarino D;Fleming E;Fire A;Dadras SS
通讯作者：
Dadras SS
影响因子：
2.9
作者：
BLUM, H;BEIER, H;GROSS, HJ
通讯作者：
GROSS, HJ
DOI：
10.1007/978-94-007-5590-1_6
发表时间：
2013-01-01
期刊：
MICRORNA CANCER REGULATION: ADVANCED CONCEPTS, BIOINFORMATICS AND SYSTEMS BIOLOGY TOOLS
影响因子：
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作者：
Kunz, Manfred
通讯作者：
Kunz, Manfred