MiR-145, a new regulator of the DNA fragmentation factor-45 (DFF45)-mediated apoptotic network.
MiR-145, a new regulator of the DNA fragmentation factor-45 (DFF45)-mediated apoptotic network.
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MiR-145，DNA 片段因子 45 (DFF45) 介导的细胞凋亡网络的新调节因子
DOI：
10.1186/1476-4598-9-211
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发表时间：
2010-08-06
期刊：
影响因子：
37.3
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Zhang J;Guo H;Qian G;Ge S;Ji H;Hu X;Chen W
研究背景MicroRNA-145（miR-145）通过抑制靶基因的表达，在细胞增殖、分化和凋亡等过程中发挥重要作用。DNA片段化因子-45（DFF 45）是Caspase-3的底物，在细胞凋亡过程中，Caspase-3对DFF 45的切割释放DFF 40，DFF 40将染色体DNA降解为核小体片段。目前还没有关于miR-145和DFF 45基因之间关系的深入研究。ResultsIn this study，我们确定DFF 45为miR-145的新靶点。我们证明了miR-145靶向DFF 45编码序列（CDS）中的假定结合位点，并且其丰度与结肠癌细胞中DFF 45的表达呈负相关。使用荧光素酶报告系统，我们发现miR-145抑制与DFF 45的推定结合位点融合的荧光素酶报告基因的表达。miR-145降低了DFF 45蛋白的水平，但没有DFF 45 mRNA的水平，这表明了一种翻译调控机制。此外，我们证明，这种特定的沉默DFF 45的miR-145帐户，至少在一定程度上，为staurosporine诱导的肿瘤细胞aprotosisin vitro.ConclusionsOur研究揭示了以前未被认识的功能，miR-145在DFF 45的加工，这可能是癌症生物学的关键方面。
BackgroundMicroRNA-145 (miR-145) is considered to play key roles in many cellular processes, such as proliferation, differentiation and apoptosis, by inhibiting target gene expression. DNA Fragmentation Factor-45 (DFF45) has been found to be the substrate of Caspase-3, and the cleavage of DFF45 by caspase-3 during apoptosis releases DFF40 that degrades chromosomal DNA into nucleosomal fragments. There are currently no in-depth studies on the relationship between miR-145 and the DFF45 gene.ResultsIn this study, we identified DFF45 as a novel target of miR-145. We demonstrated that miR-145 targets a putative binding site in the coding sequence (CDS) of DFF45, and its abundance is inversely associated with DFF45 expression in colon cancer cells. Using a luciferase reporter system, we found that miR-145 suppresses the expression of the luciferase reporter gene fused to the putative binding site of DFF45. The level of DFF45 protein, but not DFF45 mRNA, was decreased by miR-145, suggesting a mechanism of translational regulation. Furthermore, we demonstrate that this specific silencing of DFF45 by miR-145 accounts, at least in part, for the staurosporine-induced tumor cell apoptosisin vitro.ConclusionsOur study reveals a previously unrecognized function of miR-145 in DFF45 processing, which may underlie crucial aspects of cancer biology.
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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：
8.8
作者：
Abel, F;Sjoberg, R-M;Ejeskar, K;Krona, C;Martinsson, T
通讯作者：
Martinsson, T
DOI：
10.1073/pnas.0808042106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Sachdeva, Mohit;Zhu, Shoumin;Mo, Yin-Yuan
通讯作者：
Mo, Yin-Yuan
影响因子：
64.5
作者：
Liu, XS;Zou, H;Wang, XD
通讯作者：
Wang, XD
影响因子：
64.5
作者：
Eulalio, Ana;Huntzinger, Eric;Izaurralde, Elisa
通讯作者：
Izaurralde, Elisa