Title: The oncogenic and prognostic potential of eight microRNAs identified by a synergetic regulatory network approach in lung cancer

Authors: Ramkrishna Mitra; Zhongming Zhao

Addresses: 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

Abstract: 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.

Keywords: computational biology; lung cancer; reproducible regulation; oncogenic microRNAs; patient survival; prognostic potential; synergetic regulatory networks; miRNA-TF co-regulatory networks; gene expression; molecular interactions; cellular systems; data mining; transcription factors.

DOI: 10.1504/IJCBDD.2014.066572

International Journal of Computational Biology and Drug Design, 2014 Vol.7 No.4, pp.384 - 393

Received: 07 Oct 2014
Accepted: 29 Oct 2014

Published online: 24 Dec 2014 *

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