A systematic study of critical miRNAs on cells proliferation and apoptosis by the shortest path
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RESEARCH ARTICLE
Open Access
A systematic study of critical miRNAs on cells proliferation and apoptosis by the shortest path Peng Xu1,2, Qian Wu3, Deyang Lu1, Jian Yu1, Yongsheng Rao1, Zheng Kou1, Gang Fang1, Wenbin Liu1* Henry Han4* * Correspondence: wbliu6910@ gzhu.edu.cn; [email protected] 1 Institute of computational science and technology, Guangzhou University, Guangzhou 510006, Guangdong, China 4 Department of Computer and Information Science, Fordham University, New York, NY 10023, USA Full list of author information is available at the end of the article
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Abstract Background: MicroRNAs are a class of important small noncoding RNAs, which have been reported to be involved in the processes of tumorigenesis and development by targeting a few genes. Existing studies show that the imbalance between cell proliferation and apoptosis is closely related to the initiation and development of cancers. However, the impact of miRNAs on this imbalance has not been studied systematically. Results: In this study, we first construct a cell fate miRNA-gene regulatory network. Then, we propose a systematical method for calculating the global impact of miRNAs on cell fate genes based on the shortest path. Results on breast cancer and liver cancer datasets show that most of the cell fate genes are perturbed by the differentially expressed miRNAs. Most of the top-identified miRNAs are verified in the Human MicroRNA Disease Database (HMDD) and are related to breast and liver cancers. Function analysis shows that the top 20 miRNAs regulate multiple cell fate related function modules and interact tightly based on their functional similarity. Furthermore, more than half of them can promote sensitivity or induce resistance to some anticancer drugs. Besides, survival analysis demonstrates that the top-ranked miRNAs are significantly related to the overall survival time in the breast and liver cancers group. Conclusion: In sum, this study can help to systematically study the important role of miRNAs on proliferation and apoptosis and thereby uncover the key miRNAs during the process of tumorigenesis. Furthermore, the results of this study will contribute to the development of clinical therapy based miRNAs for cancers. Keywords: miRNA, Imbalance, Proliferation, Apoptosis, Cell fate gene, Cancer
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