An Integrated Analysis of Aberrantly Expressed miRNA and mRNA Profiles Unveils a Robust Regulatory Network in HepG2 Cell

Abstract

As crucial negative regulatory small non-coding molecules, microRNAs (miRNAs), have multiple biological roles. The abnormal expression of specific miRNAs may contribute to the occurrence and development of tumor. Here, based on HepG2 and L02 cells, we attempted to demonstrate the potential regulatory network of aberrantly expressed miRNA profiles, interaction between miRNA and mRNA, and potential functional correlation between different miRNAs. De-regulated miRNA and mRNA expression profiles were completely surveyed and identified by applying deep sequenc-ing and microarray techniques, respectively. The genome-wide and integrative analysis of miRNA-mRNA was performed based on their functional relationship according to experimentally validated and predicted targets. Nearly 50% targets were negatively regulated by at least 2 aberrantly expressed miRNAs. Similar results were obtained based on experimentally validated and predicted targets. Compared with abnormal miRNAs, their targets showed various expression patterns: stably expressed, down-regulated or up-regulated. Although the theoretical potential miRNA-mRNA interaction could be predicted, they showed consistent or inconsistent expression patterns. Both functional enrichment analysis of target mRNAs of dysregulated miRNAs and abnormal mRNA profiles suggested that corresponding pathways were involved in tumorigenesis. Moreover, to obtain potential functional relationships between different miRNAs, we also performed expression analysis of homologous miRNAs in gene families. Generally, they could co-regulate biological processes with similar roles. The integrative analysis of miRNA-mRNA indicated a complex and flexible regulatory network. The robust network mainly derived from multiple targets for a specific miRNA (and vice versa), each mRNA and co-regulation roles of different miRNAs.

Share and Cite:

Yang, S. , Zhang, H. , Guo, L. , Zhao, Y. and Chen, F. (2013) An Integrated Analysis of Aberrantly Expressed miRNA and mRNA Profiles Unveils a Robust Regulatory Network in HepG2 Cell. Engineering, 5, 53-56. doi: 10.4236/eng.2013.510B011.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] E. Enerly, I. Steinfeld, K. Kleivi, S. K. Leivonen, M. R. Aure, H. G. Russnes, J. A. Ronneberg, H. Johnsen, R. Navon, E. Rodland, R. Makela, B. Naume, M. Perala, O. Kallioniemi, V. N. Kristensen, Z. Yakhini and A. L. Borresen-Dale, “miRNA-mRNA Integrated Analysis Reveals Roles for miRNAs in Primary Breast Tumors,” PLoS One, Vol. 6, 2011, Article ID: e16915. http://dx.doi.org/10.1371/journal.pone.0016915
[2] F. Xie, P. Xiao, D. Chen, L. Xu and B. Zhang, “miRDeep Finder: A miRNA Analysis Tool for Deep Sequencing of Plant Small RNAs,” Plant Molecular Biology, 2012.
[3] D. P. Bartel, “MicroRNAs: Target Recognition and Regulatory Functions,” Cell, Vol. 136, 2009, pp. 215-233. http://dx.doi.org/10.1016/j.cell.2009.01.002
[4] C. Vaz, H. M. Ahmad, P. Sharma, R. Gupta, L. Kumar, R. Kulshreshtha and A. Bhattacharya, “Analysis of micro-RNA Transcriptome by Deep Sequencing of Small RNA Libraries of Peripheral Blood,” BMC Genomics, Vol. 11, 2010, p. 288. http://dx.doi.org/10.1186/1471-2164-11-288
[5] J. A. Bro-derick, W. E. Salomon, S. P. Ryder, N. Aronin and P. D. Zamore, “Argonaute Protein Identity and Pairing Geometry Determine Cooperativity in Mammalian RNA Silencing,” RNA—A Publication of the RNA Society, Vol. 17, 2011, pp. 1858-1869. http://dx.doi.org/10.1261/rna.2778911
[6] F. M. Buffa, C. Camps, L. Winchester, C. E. Snell, H. E. Gee, H. Sheldon, M. Taylor, A. L. Harris and J. Ragoussis, “microRNA-Associated Progression Pathways and Potential Therapeutic Targets Identified by Integrated mRNA and microRNA Expression Profiling in Breast Cancer,” Cancer Research, Vol. 71, 2011, pp. 5635-5645. http://dx.doi.org/10.1158/0008-5472.CAN-11-0489
[7] R. Rosell, M. A. Molina, C. Costa, S. Simonetti, A. Gimenez-Capitan, J. Bertran-Alamillo, C. Mayo, T. Moran, P. Mendez, F. Cardenal, D. Isla, M. Provencio, M. Cobo, A. Insa, R. Garcia-Campelo, N. Reguart, M. Majem, S. Viteri, E. Carcereny, R. Porta, B. Massuti, C. Queralt, I. de Aguirre, J. M. Sanchez, M. Sanchez-Ronco, J. L. Mate, A. Ariza, S. Benlloch, J. J. Sanchez, T. G. Bivona, C. L. Sawyers and M. Taron, “Pretreatment EGFR T790M Mutation and BRCA1 mRNA Expression in Erlotinib-Treated Advanced Non-Small-Cell Lung Cancer Patients with EGFR Mutations,” Clinical Cancer Research, Vol. 17, 2011, pp. 1160-1168. http://dx.doi.org/10.1158/1078-0432.CCR-10-2158
[8] A. Font, M. Taron, J. L. Gago, C. Costa, J. J. Sanchez, C. Carrato, M. Mora, P. Celiz, L. Perez, D. Rodriguez, A. Gimenez-Capitan, V. Quiroga, S. Benlloch, L. Ibarz and R. Rosell, “BRCA1 mRNA Expression and Outcome to Neoadjuvant Cisplatin-Based Chemotherapy in Bladder Cancer,” Annals of Oncology, Vol. 22, 2011, pp. 139-144. http://dx.doi.org/10.1093/annonc/mdq333
[9] A. M. Sieuwerts, B. Mostert, J. Bolt-de Vries, D. Peeters, F. E. de Jongh, J. M. Stouthard, L. Y. Dirix, P. A. van Dam, A. Van Galen, V. de Weerd, J. Kraan, P. van der Spoel, R. Ramirez-Moreno, C. H. van Deurzen, M. Smid, J. X. Yu, J. Jiang, Y. Wang, J. W. Gratama, S. Sleijfer, J. A. Foekens and J. W. Martens, “mRNA and microRNA Expression Profiles in Circulating Tumor Cells and Primary Tumors of Metastatic Breast Cancer Patients,” Clinical Cancer Research, Vol. 17, 2011, pp. 3600-3618. http://dx.doi.org/10.1158/1078-0432.CCR-11-0255
[10] H. Ogata, S. Goto, K. Sato, W. Fujibuchi, H. Bono and M. Kanehisa, “KEGG: Kyoto Encyclopedia of Genes and Genomes,” Nucleic Acids Research, Vol. 27, 1999, pp. 29-34. http://dx.doi.org/10.1093/nar/27.1.29
[11] H. Yamaguchi and J. Condeelis, “Regulation of the Actin Cytoskeleton in Cancer Cell Migration and Invasion,” Biochimica et Biophysica Acta, Vol. 1773, 2007, pp. 642-652. http://dx.doi.org/10.1016/j.bbamcr.2006.07.001
[12] A. Lachenmayer, C. Alsinet, R. Savic, L. Cabellos, S. Toffanin, Y. Hoshida, A. Villanueva, B. Minguez, P. Newell, H. W. Tsai, J. Barretina, S. Thung, S. C. Ward, J. Bruix, V. Mazzaferro, M. Schwartz, S. L. Friedman and J. M. Llovet, “Wnt-Pathway Activation in Two Molecular Classes of Hepatocellular Carcinoma and Experimental Modulation by Sorafenib,” Clinical Cancer Research, Vol. 18, 2012, pp. 4997-5007. http://dx.doi.org/10.1158/1078-0432.CCR-11-2322

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.