This article is part of the supplement: Twelfth International Conference on Bioinformatics (InCoB2013): Computational Biology
Co-modulated behavior and effects of differentially expressed miRNA in colorectal cancer
- Equal contributors
1 Department of Surgery, Veterans General Hospital, Taipei, Taiwan
2 Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
3 Bioinformatics Center, Chang Gung University, Taoyuan, Taiwan
4 Department of Biotechnology and Laboratory Science in Medicine and Institute of Biotechnology in Medicine, National Yang Ming University, Taipei, Taiwan
5 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
6 Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
7 Department of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
8 Clinical Genomics & Proteomics Core Laboratory, Department of medical research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
9 Genomics Research Center, Academia Sinica, Taipei, Taiwan
10 Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
11 School of Medicine, Yang-Ming University, Taipei, Taiwan
BMC Genomics 2013, 14(Suppl 5):S12 doi:10.1186/1471-2164-14-S5-S12Published: 16 October 2013
MicroRNAs (miRNAs) are short noncoding RNAs (approximately 22 nucleotides in length) that play important roles in colorectal cancer (CRC) progression through silencing gene expression. Numerous dysregulated miRNAs simultaneously participate in the process of colon cancer development. However, the detailed mechanisms and biological functions of co-expressed miRNA in colorectal carcinogenesis have yet to be fully elucidated.
The objective of this study was to identify the dysfunctional miRNAs and their target mRNAs using a wet-lab experimental and dry-lab bioinformatics approach. The differentially expressed miRNA candidates were identified from 2 miRNA profiles, and were confirmed in CRC clinical samples using reported target genes of dysfunctional miRNAs to perform functional pathway enrichment analysis. Potential target gene candidates were predicted by an in silico search, and their expression levels between normal and colorectal tumor tissues were further analyzed using real-time polymerase chain reaction (RT-PCR).
We identified 5 miRNAs (miR-18a, miR-31, miR-96, miR-182, and miR-224) and 10 miRNAs (miR-1, miR-9, miR-10b, miR-133a, miR-143, miR-137, miR-147b, miR-196a/b, and miR-342) that were significantly upregulated and downregulated in colon tumors, respectively. Bioinformatics analysis showed that the known targets of these dysregulated miRNAs simultaneously participated in epithelial-to-mesenchymal transition (EMT), cell growth, cell adhesion, and cell cycles. In addition, we identified that several pivotal target gene candidates may be comodulated by dysfunctional miRNAs during colon cancer progression. Finally, 7 candidates were proven to be differentially expressed, and had an anti-correlationship with dysregulated miRNA in 48 CRC samples.
Fifteen dysfunctional miRNAs were engaged in metastasis-associated pathways through comodulating 7 target genes, which were identified by using a multi-step approach. The roles of these candidate genes are worth further exploration in the progression of colon cancer, and could potentially be targets in future therapy.