微小RNA对癌基因调控的预测及初步验证

Prediction and preliminary validation of oncogene regulation by miRNAs.

作者信息

Koscianska Edyta, Baev Vesselin, Skreka Konstantinia, Oikonomaki Katerina, Rusinov Ventsislav, Tabler Martin, Kalantidis Kriton

机构信息

Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, PO Box 1385, GR-71110, Heraklion/Crete, Greece.

出版信息

BMC Mol Biol. 2007 Sep 18;8:79. doi: 10.1186/1471-2199-8-79.

Abstract

BACKGROUND

MicroRNAs (miRNAs) are one of the most abundant groups of regulatory genes in multicellular organisms, playing important roles in many fundamental cellular processes. More than four hundred miRNAs have been identified in humans and the deregulation of miRNA expression has been also shown in many cancers. Despite the postulated involvement of miRNAs in tumourigenesis, there are only a few examples where an oncogene or a tumour suppressor has been identified as a miRNA target.

RESULTS

Here, we present an in silico analysis of potential miRNA- oncogene interactions. Moreover, we have tested the validity of two possible interactions of miRNAs with genes related to cancer. We present evidence for the down-regulation of c-MYC, one of the most potent and frequently deregulated oncogenes, by let-7 miRNA, via the predicted binding site in the 3'UTR, and verify the suppression of BCL-2 by miR16.

CONCLUSION

In this work both bioinformatic and experimental approaches for the prediction and validation of possible targets for miRNAs have been used. A list of putative targets for different oncomirs, validation of which would be of special interest, is proposed and two such interactions have been experimentally validated.

摘要

背景

微小RNA(miRNA)是多细胞生物中最丰富的调控基因群体之一,在许多基本细胞过程中发挥重要作用。在人类中已鉴定出四百多种miRNA,并且在许多癌症中也显示出miRNA表达失调。尽管推测miRNA参与肿瘤发生,但只有少数例子表明癌基因或肿瘤抑制基因被确定为miRNA的靶标。

结果

在此,我们对潜在的miRNA-癌基因相互作用进行了计算机分析。此外,我们测试了miRNA与癌症相关基因的两种可能相互作用的有效性。我们提供了证据,证明let-7 miRNA通过3'非翻译区(3'UTR)中的预测结合位点下调c-MYC(最强大且最常失调的癌基因之一),并验证了miR16对BCL-2的抑制作用。

结论

在这项工作中,使用了生物信息学和实验方法来预测和验证miRNA的可能靶标。提出了不同致癌miRNA的假定靶标列表,对其进行验证将具有特殊意义,并且已通过实验验证了两种此类相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ae/2096627/8c8b48045197/1471-2199-8-79-1.jpg

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