MicroRNAs 10a and 10b are potent inducers of neuroblastoma cell differentiation through targeting of nuclear receptor corepressor 2.
MicroRNAs 10a and 10b are potent inducers of neuroblastoma cell differentiation through targeting of nuclear receptor corepressor 2.
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DOI：
10.1038/cdd.2010.172
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发表时间：
2011-07
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
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microRNA作为转录后基因表达的负调控因子，在细胞分化中发挥重要作用。几种神经母细胞瘤细胞系可以通过全反式维甲酸（ATRA）诱导分化，并用于模拟参与这一过程的信号通路。为了鉴定有助于分化的miRNAs，我们分析了ATRA处理神经母细胞瘤细胞系后的364个位点，发现miR-10a和miR-10 b在SK-N-BE、LAN 5和SHSY-5 Y中高度过表达。这些miRNAs的异位过表达导致转录组的主要重编程和分化表型，这与ATRA在这些细胞系中诱导的表型相似。预测的下调的miR-10 a/B靶点之一是核受体辅阻遏物2（NCOR 2），其是已知抑制神经突生长的基因转录的辅阻遏物。NCOR 2被实验验证为miR-10 a/B的直接靶点，并且单独使用SiRNA介导的该mRNA抑制会导致神经细胞分化。此外，分化的诱导可以通过使用缺乏miR-10 a/B 3' UTR靶位点的表达构建体异位上调NCOR 2来阻断。我们得出的结论是，miR-10 a/B通过直接靶向NCOR 2在神经细胞分化过程中发挥重要作用，这反过来又诱导了一系列初级和二级转录改变，包括MYCN的下调。
MicroRNAs function as negative regulators of post-transcriptional gene expression, playing major roles in cellular differentiation. Several neuroblastoma cell lines can be induced to undergo differentiation by all-trans-retinoic acid (ATRA) and are used for modelling signalling pathways involved in this process. To identify miRNAs contributing to differentiation, we profiled 364 loci following ATRA treatment of neuroblastoma cell lines and found miR-10a and miR-10b to be highly over-expressed in SK-N-BE, LAN5, and SHSY-5Y. Ectopic over-expression of these miRNAs led to a major reprogramming of the transcriptome and a differentiated phenotype that was similar to that induced by ATRA in each of these cell lines. One of the predicted down-regulated miR-10a/b targets was nuclear receptor co-repressor 2 (NCOR2), a co-repressor of gene transcription which is known to suppress neurite outgrowth. NCOR2 was experimentally validated as a direct target of miR-10a/b, and siRNA mediated inhibition of this mRNA alone resulted in neural cell differentiation. Moreover, induction of differentiation could be blocked by ectopic up-regulation of NCOR2 using an expression construct lacking the miR-10a/b 3’ UTR target site. We conclude that miR-10a/b play major roles in the process of neural cell differentiation through direct targeting of NCOR2, which in turn induces a cascade of primary and secondary transcriptional alterations, including the down-regulation of MYCN.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
46.9
作者：
Ma L;Reinhardt F;Pan E;Soutschek J;Bhat B;Marcusson EG;Teruya-Feldstein J;Bell GW;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
64.8
作者：
Jepsen, Kristen;Solum, Derek;Rosenfeld, Michael G.
通讯作者：
Rosenfeld, Michael G.
DOI：
10.1073/pnas.0700071104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Laneve, Pietro;Di Marcotullio, Lucia;Caffarelli, Elisa
通讯作者：
Caffarelli, Elisa
影响因子：
64.8
作者：
CHEN, JD;EVANS, RM
通讯作者：
EVANS, RM