Co-modulated behavior and effects of differentially expressed miRNA in colorectal cancer
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- 作者：Wei-Shone Chen (33)
Ting-Wen Chen (34) (35)
Tzu-Hsien Yang (36)
Ling-Yueh Hu (37)
Hung-Wei Pan (38)
Chung-Man Leung (39)
Sung-Chou Li (40)
Meng-Ru Ho (41)
Chih-Wen Shu (38)
Pei-Feng Liu (38)
Shou-Yu Yu (38)
Ya-Ting Tu (38)
Wen-Chang Lin (37)
Tony T Wu (42) (43)
Kuo-Wang Tsai (38) - 关键词：microRNA ; colorectal cancer ; pathway enrichment analysis
- 刊名：BMC Genomics
- 出版年：2013
- 出版时间：October 2013
- 年：2013
- 卷：14
- 期：5-supp
- 全文大小：
- 作者单位：Wei-Shone Chen (33)
Ting-Wen Chen (34) (35)
Tzu-Hsien Yang (36)
Ling-Yueh Hu (37)
Hung-Wei Pan (38)
Chung-Man Leung (39)
Sung-Chou Li (40)
Meng-Ru Ho (41)
Chih-Wen Shu (38)
Pei-Feng Liu (38)
Shou-Yu Yu (38)
Ya-Ting Tu (38)
Wen-Chang Lin (37)
Tony T Wu (42) (43)
Kuo-Wang Tsai (38)
33. Department of Surgery, Veterans General Hospital, Taipei, Taiwan
34. Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
35. Bioinformatics Center, Chang Gung University, Taoyuan, Taiwan
36. Department of Biotechnology and Laboratory Science in Medicine and Institute of Biotechnology in Medicine, National Yang Ming University, Taipei, Taiwan
37. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
38. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
39. Department of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
40. Clinical Genomics & Proteomics Core Laboratory, Department of medical research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
41. Genomics Research Center, Academia Sinica, Taipei, Taiwan
42. Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
43. School of Medicine, Yang-Ming University, Taipei, Taiwan - ISSN：1471-2164
文摘
Background 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. Results 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. Conclusion 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.