Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Nat Struct Mol Biol. 2013 Nov;20(11):1325-32. doi: 10.1038/nsmb.2678. Epub 2013 Oct 6.
Little is known about the extent to which individual microRNAs (miRNAs) regulate common processes of tumor biology across diverse cancer types. Using molecular profiles of >3,000 tumors from 11 human cancer types in The Cancer Genome Atlas, we systematically analyzed expression of miRNAs and mRNAs across cancer types to infer recurrent cancer-associated miRNA-target relationships. As we expected, the inferred relationships were consistent with sequence-based predictions and published data from miRNA perturbation experiments. Notably, miRNAs with recurrent target relationships were frequently regulated by genetic and epigenetic alterations across the studied cancer types. We also identify new examples of miRNAs that coordinately regulate cancer pathways, including the miR-29 family, which recurrently regulates active DNA demethylation pathway members TET1 and TDG. The online resource http://cancerminer.org allows exploration and prioritization of miRNA-target interactions that potentially regulate tumorigenesis.
人们对于个体 microRNAs（miRNAs）在多大程度上调节不同癌症类型中常见的肿瘤生物学过程知之甚少。利用癌症基因组图谱中 11 种人类癌症类型的 >3000 个肿瘤的分子图谱，我们系统地分析了 miRNA 和 mRNAs 在癌症类型中的表达，以推断反复出现的癌症相关 miRNA-靶关系。正如我们所料，推断出的关系与基于序列的预测以及 miRNA 干扰实验的已发表数据一致。值得注意的是，在研究的癌症类型中，具有反复靶关系的 miRNA 经常受到遗传和表观遗传改变的调节。我们还发现了新的 miRNA 协调调节癌症途径的例子，包括 miR-29 家族，它反复调节活性 DNA 去甲基化途径成员 TET1 和 TDG。在线资源 http://cancerminer.org 允许探索和优先考虑可能调节肿瘤发生的 miRNA-靶相互作用。
