Comparative Analysis of microRNA Binding Site Distribution and microRNA-Mediated Gene Expression Repression of Oncogenes and Tumor Suppressor Genes.

Comparative Analysis of microRNA Binding Site Distribution and microRNA-Mediated Gene Expression Repression of Oncogenes and Tumor Suppressor Genes.
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DOI:
10.3390/genes13030481
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发表时间:
2022-03-09
期刊:
影响因子:
3.5
通讯作者:
Wang D
Wang D
中科院分区:
生物学3区
文献类型:
--
作者:
Tian S;Wang J;Zhang F;Wang D

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microRNA(miRNAs)是一类短的非编码RNA家族,可调控人类基因组一半以上的基因表达水平。先前关于miRNA在癌症中的作用的研究表明,总体上广泛的miRNA下调是人类癌症的标志,尽管单个miRNA可以是肿瘤抑制和致癌的,并且推测癌症基因更容易被miRNA靶向。然而,癌基因和肿瘤抑制基因(TSG)受miRNA控制的程度还没有比较。为了实现这一目标,我们构建了癌基因和TSGs的列表,并将它们彼此进行比较,并与整个蛋白质编码基因群体进行比较,在miRNA结合位点分布和表达水平变化方面对miRNA产生的遗传破坏进行比较。正如预期的那样,结果显示癌基因mRNA锚更多的miRNA结合位点,并且在mRNA丰度和翻译效率水平上比整个蛋白质编码基因群体处于更高程度的miRNA介导的抑制下。重要的是,平均而言,TSG mRNA比癌基因mRNA更高度地被miRNA靶向和调节。据我们所知,这是首次比较癌基因和TSGs的miRNA调控。
MicroRNAs (miRNAs) are a family of short, noncoding RNAs that can regulate gene expression levels of over half of the human genome. Previous studies on the role of miRNAs in cancer showed overall widespread downregulation of miRNAs as a hallmark of human cancer, though individual miRNAs can be both tumor suppressive and oncogenic, and cancer genes are speculated to be more targeted by miRNA. However, the extents to which oncogenes and tumor suppressor genes (TSG) are controlled by miRNA have not been compared. To achieve this goal, we constructed lists of oncogenes and TSGs and compared them with each other, and with the whole protein-coding gene population, in terms of miRNA binding sites distribution and expression level changes upon genetic disruption of miRNA production. As expected, the results show that cancer gene mRNAs anchor more miRNA binding sites, and are under a higher degree of miRNA-mediated repression at both mRNA abundance and translation efficiency levels than the whole protein-coding gene population. Importantly, on average, TSG mRNAs are more highly targeted and regulated by miRNA than oncogene mRNAs. To the best of our knowledge, this is the first comparison of miRNA regulation of oncogenes and TSGs.
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