C-Myc functions as a competing endogenous RNA in acute promyelocytic leukemia.
C-Myc functions as a competing endogenous RNA in acute promyelocytic leukemia.
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C-Myc 在急性早幼粒细胞白血病中充当竞争性内源性 RNA
DOI：
10.18632/oncotarget.10896
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发表时间：
2016-08-30
期刊：
影响因子：
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通讯作者：
Wang SY
中科院分区：
文献类型：
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作者：
Ding Y;Wang ZC;Zheng Y;Hu Z;Li Y;Luo DF;Wang SY
最近的报道描述了一种新的转录后调控，RNA转录产物可以通过竞争它们共同的microRNAs而相互干扰。这些被称为竞争内源RNAs(CeRNAs)的RNA转录本调节其靶标上miRNAs的分布。CERNA相互作用的一个推论是，急性早幼粒细胞白血病(APL)中的染色体易位会由于3‘UTRs表达的改变而扰乱CERNA的调节。在我们的研究中，我们证明了与APL相关的融合癌基因PML/RARα的表达受到c-Myc mRNA转录的抑制，而不是蛋白质编码功能，而是依赖于microRNA。C-Myc转录本的减弱导致APL细胞中PML/RARα降解的细胞表型，但这些与Myc还原相关的细胞表型足以以microRNA依赖的方式被取消。我们还发现，let-7microRNA家族成员促进了全反式维甲酸诱导的NB4细胞的分化，并且c-Myc和PML/RARα的表达水平通过改变miRNA靶点来影响它们的活性。这些结果表明，c-Myc mRNA通过改变let-7miRNAs在靶细胞上的分布来抑制PML/RARα的表达。我们的发现揭示了c-Myc作为APL中PML/RARα的潜在CENA的一个先前未被认识的作用。
Recent reports have described a new post-transcriptional regulation that RNA transcripts can crosstalk with each other by competing for their common microRNAs. These RNA transcripts termed competing endogenous RNAs (ceRNAs) regulate the distribution of miRNAs on their targets. One corollary from ceRNA interaction is that chromosomal translocation in acute promyelocytic leukemia (APL) would perturb ceRNA regulation due to altered expression of 3′UTRs. In our study, we demonstrate that expression of PML/RARα, the APL-associated fusion oncogene is repressed by c-Myc mRNA transcript independent of protein-coding function but dependent upon microRNA. Attenuation of c-Myc transcript results in PML/RARα-degraded cellular phenotypes in APL cells, but these Myc reduction-associated cell phenotypes are sufficient to abrogate in a microRNA dependent manner. We also show that let-7 microRNA family members promote differentiation of All-Trans-Retinoic Acid (ATRA)-induced NB4 cells and their activities are affected by expression levels of both c-Myc and PML/RARα through altering miRNA targets. These results indicate that c-Myc mRNA represses PML/RARα expression via altering the distribution of let-7 miRNAs on their targets. Our findings reveal a previously unrecognized role of c-Myc as a potential ceRNA for PML/RARα in APL.