Mitra Ramkrishna, Zhao Zhongming
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Departments of Biomedical Informatics, Psychiatry, and Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Int J Comput Biol Drug Des. 2014;7(4):384-93. doi: 10.1504/IJCBDD.2014.066572. Epub 2014 Dec 25.
Transcription factors (TFs) and microRNAs (miRNAs), the two main gene regulators in the biological system, control the gene expression at the transcriptional and post-transcriptional level, respectively. However, little is known regarding whether the miRNATF co-regulatory mechanisms, predicted by several studies, truly reflect the molecular interactions in cellular systems. To tackle this important issue, we developed an integrative framework by utilising four independent miRNA and matched mRNA expression profiling datasets to identify reproducible regulations, and demonstrated this approach in non-small cell lung cancer (NSCLC). Our analyses pinpointed several reproducible miRNA-TF co-regulatory networks in NSCLC from which we systematically prioritised eight hub miRNAs that may have strong oncogenic characteristics. Here, we discussed the major findings of our study and explored the oncogenic and prognostic potential of eight prioritised miRNAs through literature-mining based analysis and patient survival analysis. The findings provide additional insights into the miRNA-TF co-regulation in lung cancer.
转录因子（TFs）和微小RNA（miRNAs）是生物系统中的两种主要基因调节因子，分别在转录水平和转录后水平控制基因表达。然而，关于几项研究预测的miRNA-TF共同调节机制是否真的反映了细胞系统中的分子相互作用，目前所知甚少。为了解决这个重要问题，我们开发了一个综合框架，利用四个独立的miRNA和匹配的mRNA表达谱数据集来识别可重复的调节，并在非小细胞肺癌（NSCLC）中展示了这种方法。我们的分析确定了NSCLC中几个可重复的miRNA-TF共同调节网络，从中我们系统地筛选出了八个可能具有强大致癌特征的关键miRNA。在此，我们讨论了研究的主要发现，并通过基于文献挖掘的分析和患者生存分析，探索了八个筛选出的miRNA的致癌和预后潜力。这些发现为肺癌中的miRNA-TF共同调节提供了更多见解。
