全部 标题 作者
关键词 摘要


MicroRNA Response Elements-Mediated miRNA-miRNA Interactions in Prostate Cancer

DOI: 10.1155/2012/839837

Full-Text   Cite this paper   Add to My Lib

Abstract:

The cell is a highly organized system of interacting molecules including proteins, mRNAs, and miRNAs. Analyzing the cell from a systems perspective by integrating different types of data helps revealing the complexity of diseases. Although there is emerging evidence that microRNAs have a functional role in cancer, the role of microRNAs in mediating cancer progression and metastasis remains not fully explored. As the amount of available miRNA and mRNA gene expression data grows, more systematic methods combining gene expression and biological networks become necessary to explore miRNA function. In this work I integrated functional miRNA-target interactions with mRNA and miRNA expression to infer mRNA-mediated miRNA-miRNA interactions. The inferred network represents miRNA modulation through common targets. The network is used to characterize the functional role of microRNA response element (MRE) to mediate interactions between miRNAs targeting the MRE. Results revealed that miRNA-1 is a key player in regulating prostate cancer progression. 11 miRNAs were identified as diagnostic and prognostic biomarkers that act as tumor suppressor miRNAs. This work demonstrates the utility of a network analysis as opposed to differential expression to find important miRNAs that regulate prostate cancer. 1. Introduction MicroRNAs (miRNAs) are small (18–24) nucleotide long noncoding RNAs that play a major regulatory role in a broad range of biological processes and complex diseases. Since the discovery of microRNAs [1], they emerged as a new layer of gene regulation that dramatically influence genes by binding to its 3′UTR and inactivate it by promoting its degradation or translational repression [2]. Computational predictions estimated that there are around 1700 miRNAs in human and each targets hundreds of mRNAs and over 50% of the human protein coding genes are regulated by miRNAs [3]. The area of miRNA genetics has rapidly expanded from identifying miRNAs to exploring their function and their potential as therapeutic options. Several studies have demonstrated that miRNAs are key players in the initiation and progression of cancer including prostate cancer and they act as oncogenes and tumor suppressors [4–6]. Examination of prostate tumor miRNA expression has revealed widespread dysregulation of miRNAs in primary and metastatic compared with normal prostate tissue [7]. Profiling miRNAs in various types of cancer provided evidence that miRNAs are diagnostic and prognostic biomarkers [8] that may stratify prostate tumors based on specific genetic profiles and thereby

References

[1]  G. Ruvkun, “Molecular biology: glimpses of a tiny RNA world,” Science, vol. 294, no. 5543, pp. 797–799, 2001.
[2]  S. Sevli, A. Uzumcu, M. Solak, M. Ittmann, and M. Ozen, “The function of microRNAs, small but potent molecules, in human prostate cancer,” Prostate Cancer and Prostatic Diseases, vol. 13, no. 3, pp. 208–217, 2010.
[3]  A. Gordanpour, R. K. Nam, L. Sugar, and A. Seth, “MicroRNAs in prostate cancer: from biomarkers to molecularly-based therapeutics,” Prostate Cancer and Prostatic Diseases, vol. 1, p. 6, 2012.
[4]  L. He and G. J. Hannon, “MicroRNAs: small RNAs with a big role in gene regulation,” Nature Reviews Genetics, vol. 5, no. 8, p. 631, 2004.
[5]  Y. Pang, C. Y. F. Young, and H. Yuan, “MicroRNAs and prostate cancer,” Acta Biochimica et Biophysica Sinica, vol. 42, no. 6, pp. 363–369, 2010.
[6]  B. Zhang, X. Pan, G. P. Cobb, and T. A. Anderson, “microRNAs as oncogenes and tumor suppressors,” Developmental Biology, vol. 302, no. 1, pp. 1–12, 2007.
[7]  G. A. Calin and C. M. Croce, “MicroRNA signatures in human cancers,” Nature Reviews Cancer, vol. 6, no. 11, pp. 857–866, 2006.
[8]  S. D. Hsu, F. M. Lin, W. Y. Wu et al., “Mirtarbase: a database curates experimentally validated microRNA-target interactions,” Nucleic Acids Research, vol. 39, no. 1, pp. D163–D169, 2011.
[9]  A. Esquela-Kerscher and F. J. Slack, “Oncomirs-microRNAs with a role in cancer,” Nature Reviews Cancer, vol. 6, no. 4, pp. 259–269, 2006.
[10]  M. Ozen, C. J. Creighton, M. Ozdemir, and M. Ittmann, “Widespread deregulation of microRNA expression in human prostate cancer,” Oncogene, vol. 27, no. 12, pp. 1788–1793, 2008.
[11]  A. Grimson, K. K. H. Farh, W. K. Johnston, P. Garrett-Engele, L. P. Lim, and D. P. Bartel, “MicroRNA targeting specificity in mammals: determinants beyond seed pairing,” Molecular Cell, vol. 27, no. 1, pp. 91–105, 2007.
[12]  A. Krek, D. Grün, M. N. Poy et al., “Combinatorial microRNA target predictions,” Nature Genetics, vol. 37, no. 5, pp. 495–500, 2005.
[13]  J. I. Satoh and H. Tabunoki, “Comprehensive analysis of human microRNA target networks,” Biodata Mining, vol. 4, no. 1, p. 17, 2011.
[14]  V. Jayaswal, M. Lutherborrow, D. D. F. Ma, and Y. H. Yang, “Identification of microRNA-mRNA modules using microarray data,” BMC Genomics, vol. 12, p. 138, 2011.
[15]  J. C. Huang, T. Babak, T. W. Corson et al., “Using expression profiling data to identify human microRNA targets,” Nature Methods, vol. 4, no. 12, pp. 1045–1049, 2009.
[16]  L. Poliseno, L. Salmena, J. Zhang, B. Carver, W. J. Haveman, and P. P. Pandolfi, “A coding-independent function of gene and pseudogene mRNAs regulates tumour biology,” Nature, vol. 465, no. 7301, pp. 1033–1038, 2010.
[17]  P. Sumazin, X. Yang, H.-S. Chiu et al., “An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma,” Cell, vol. 147, no. 2, pp. 370–381, 2011.
[18]  M. Smoot, K. Ono, J. Ruscheinski, P. Wang, and T. Ideker, “Cytoscape 2.8: new features for data integration and network visualization,” Bioinformatics, vol. 27, no. 3, pp. 431–432, 2011.
[19]  D. Merico, R. Isserlin, O. Stueker, A. Emili, and G. D. Bader, “Enrichment map: a network-based method for gene-set enrichment visualization and interpretation,” PLos one, vol. 15, no. 11, p. e13984, 2010.
[20]  F. Xiao, Z. Zuo, G. Cai, S. Kang, X. Gao, and T. Li, “Mirecords: an integrated resource for microRNA-target interactions,” Nucleic Acids Research, vol. 37, no. 1, pp. D105–D110, 2009.
[21]  B. S. Taylor, N. Schultz, H. Hieronymus et al., “Integrative genomic profiling of human prostate cancer,” Cancer Cell, vol. 18, no. 1, pp. 11–22, 2010.
[22]  S. Wach, E. Nolte, J. Szczyrba et al., “MicroRNA profiles of prostate carcinoma detected by multiplatform microRNA screening,” International Journal of Cancer, vol. 130, pp. 611–621, 2012.
[23]  V. G. Tusher, R. Tibshirani, and G. Chu, “Significance analysis of microarrays applied to the ionizing radiation response,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 9, pp. 5116–5121, 2001.
[24]  J. J. Hornberg, F. J. Bruggeman, H. V. Westerhoff, and J. Lankelma, “Cancer: a systems biology disease,” Biosystems, vol. 83, no. 2-3, pp. 81–90, 2006.
[25]  R. S. Hudson, M. Yi, D. Esposito et al., et al., “MicroRNA-1 is a candidate tumor suppressor and prognostic marker in human prostate cancer,” Nucleic Acids Research, vol. 40, no. 8, pp. 3689–3703, 2012.

Full-Text

comments powered by Disqus