Functional analysis of microRNA and transcription factor synergistic regulatory network based on identifying regulatory motifs in non-small cell lung cancer

BMC Systems Biology

Yan Xu²  Zhiqiang Chang²  Rui Zhang²  Fujun Qiu²  Desi Shang²  Yuanshuai Zhou²  Yongjing Liu²  Yaoqun Xu¹  Ning Zhao²  Zihui Li²  Kening Li² 

[1] Institute of System Engineering, Harbin University of Commerce, Harbin 150028, China;College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China

关键词: Non-small cell lung cancer;    miR-17 family;    Cell cycle;    Motif;    Transcription factor;    MicroRNA;    Regulatory network;   

Others  :  1141817
DOI  :  10.1186/1752-0509-7-122

 received in 2013-06-10, accepted in 2013-11-04,  发布年份 2013

【 摘 要 】

Background

Lung cancer, especially non-small cell lung cancer, is a leading cause of malignant tumor death worldwide. Understanding the mechanisms employed by the main regulators, such as microRNAs (miRNAs) and transcription factors (TFs), still remains elusive. The patterns of their cooperation and biological functions in the synergistic regulatory network have rarely been studied.

Results

Here, we describe the first miRNA-TF synergistic regulation network in human lung cancer. We identified important regulators (MYC, NFKB1, miR-590, and miR-570) and significant miRNA-TF synergistic regulatory motifs by random simulations. The two most significant motifs were the co-regulation of miRNAs and TFs, and TF-mediated cascade regulation. We also developed an algorithm to uncover the biological functions of the human lung cancer miRNA-TF synergistic regulatory network (regulation of apoptosis, cellular protein metabolic process, and cell cycle), and the specific functions of each miRNA-TF synergistic subnetwork. We found that the miR-17 family exerted important effects in the regulation of non-small cell lung cancer, such as in proliferation and cell cycle regulation by targeting the retinoblastoma protein (RB1) and forming a feed forward loop with the E2F1 TF. We proposed a model for the miR-17 family, E2F1, and RB1 to demonstrate their potential roles in the occurrence and development of non-small cell lung cancer.

Conclusions

This work will provide a framework for constructing miRNA-TF synergistic regulatory networks, function analysis in diseases, and identification of the main regulators and regulatory motifs, which will be useful for understanding the putative regulatory motifs involving miRNAs and TFs, and for predicting new targets for cancer studies.

【 授权许可】

   
2013 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

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