H-ferritin-regulated microRNAs modulate gene expression in K562 cells.
H-ferritin-regulated microRNAs modulate gene expression in K562 cells.
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DOI：
10.1371/journal.pone.0122105
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Costanzo F
中科院分区：
文献类型：
--
作者：
Biamonte F;Zolea F;Bisognin A;Di Sanzo M;Saccoman C;Scumaci D;Aversa I;Panebianco M;Faniello MC;Bortoluzzi S;Cuda G;Costanzo F
在以前的研究中，我们发现，沉默的重亚基（FHC）oferritin，在细胞中的中央铁储存分子，是伴随着全球基因表达的修改。在这项工作中，我们探讨了不同的FHC量是否可以调节K562细胞中的miRNA表达水平，并研究了miRNA在基因表达谱修饰中的影响。为此，我们在沉默FHC的K562（K562 shFHC）中进行了miRNA-mRNA整合分析，将其与用乱序RNA转导的K562（K562 shRNA）进行比较。hsa-let-7 g、hsa-let-7 f、hsa-let-7i和hsa-miR-125 b在沉默细胞中显著上调。FHC表达拯救后，这些miRNA的显著下调支持FHC沉默和miRNA调节之间的特定关系。将靶预测与miRNA和基因表达谱相结合，鉴定了一个调控网络，其中包括FHC沉默上调的miRNA，以及91个下调的推定靶基因。这些基因进一步分为9个网络;得分最高的网络“细胞死亡和存活，血液系统发育和功能，造血”由18个焦点分子组成，包括RAF 1和ERK 1/2。我们证实，FHC沉默后，ERK 1/2磷酸化严重受损，RAF 1 mRNA显著下调。综上所述，我们的数据表明，在我们的实验模型中，FHC沉默可能会影响RAF 1/pERK 1/2水平，通过一组特定的miRNA的调制和铁稳态和miRNA之间的关系增加新的见解。
In a previous study, we showed that the silencing of the heavy subunit (FHC) offerritin, the central iron storage molecule in the cell, is accompanied by a modification in global gene expression. In this work, we explored whether different FHC amounts might modulate miRNA expression levels in K562 cells and studied the impact of miRNAs in gene expression profile modifications. To this aim, we performed a miRNA-mRNA integrative analysis in K562 silenced for FHC (K562shFHC) comparing it with K562 transduced with scrambled RNA (K562shRNA). Four miRNAs, namely hsa-let-7g, hsa-let-7f, hsa-let-7i and hsa-miR-125b, were significantly up-regulated in silenced cells. The remarkable down-regulation of these miRNAs, following FHC expression rescue, supports a specific relation between FHC silencing and miRNA-modulation. The integration of target predictions with miRNA and gene expression profiles led to the identification of a regulatory network which includes the miRNAs up-regulated by FHC silencing, as well as91 down-regulated putative target genes. These genes were further classified in 9 networks; the highest scoring network, “Cell Death and Survival, Hematological System Development and Function, Hematopoiesis”, is composed by 18 focus molecules including RAF1 and ERK1/2. We confirmed that, following FHC silencing, ERK1/2 phosphorylation is severely impaired and that RAF1 mRNA is significantly down-regulated. Taken all together, our data indicate that, in our experimental model, FHC silencing may affect RAF1/pERK1/2 levels through the modulation of a specific set of miRNAs and add new insights in to the relationship among iron homeostasis and miRNAs.
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DOI：
10.1016/j.bbagrm.2012.06.001
发表时间：
2012-11
影响因子：
4.7
作者：
Hou, Weihong;Tian, Qing;Steuerwald, Nury M.;Schrum, Laura W.;Bonkovsky, Herbert L.
通讯作者：
Bonkovsky, Herbert L.
影响因子：
2
作者：
Akao, Yukihiro;Nakagawa, Yoshihito;Naoe, Tomoki
通讯作者：
Naoe, Tomoki
DOI：
10.1084/jem.20080285
发表时间：
2008-10-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bousquet M;Quelen C;Rosati R;Mansat-De Mas V;La Starza R;Bastard C;Lippert E;Talmant P;Lafage-Pochitaloff M;Leroux D;Gervais C;Viguié F;Lai JL;Terre C;Beverlo B;Sambani C;Hagemeijer A;Marynen P;Delsol G;Dastugue N;Mecucci C;Brousset P
通讯作者：
Brousset P
影响因子：
4.4
作者：
Di Sanzo, Maddalena;Gaspari, Marco;Faniello, Maria Concetta
通讯作者：
Faniello, Maria Concetta
影响因子：
20.3
作者：
COCCIA, EM;STELLACCI, E;BATTISTINI, A
通讯作者：
BATTISTINI, A