Co-modulated behavior and effects of differentially expressed miRNA in colorectal cancer

被引：10

作者：

Chen, Wei-Shone ^{[1
]}

Chen, Ting-Wen ^{[2
,3
]}

Yang, Tzu-Hsien ^{[4
,5
]}

Hu, Ling-Yueh ^{[6
]}

Pan, Hung-Wei ^{[7
]}

Leung, Chung-Man ^{[8
]}

Li, Sung-Chou ^{[9
,10
]}

Ho, Meng-Ru ^{[11
]}

Shu, Chih-Wen ^{[7
]}

Liu, Pei-Feng ^{[7
]}

Yu, Shou-Yu ^{[7
]}

Tu, Ya-Ting ^{[7
]}

Lin, Wen-Chang ^{[6
]}

Wu, Tony T. ^{[12
,13
]}

Tsai, Kuo-Wang ^{[7
]}

机构：

[1] Vet Gen Hosp, Dept Surg, Taipei 11217, Taiwan

[2] Chang Gung Univ, Mol Med Res Ctr, Tao Yuan, Taiwan

[3] Chang Gung Univ, Bioinformat Ctr, Tao Yuan, Taiwan

[4] Natl Yang Ming Univ, Dept Biotechnol & Lab Sci Med, Taipei 112, Taiwan

[5] Natl Yang Ming Univ, Inst Biotechnol Med, Taipei 112, Taiwan

[6] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[7] Kaohsiung Vet Gen Hosp, Dept Med Educ & Res, Kaohsiung, Taiwan

[8] Kaohsiung Vet Gen Hosp, Dept Radiat Oncol, Kaohsiung, Taiwan

[9] Kaohsiung Chang Gung Mem Hosp, Dept Med Res, Clin Genom & Prote Core Lab, Kaohsiung, Taiwan

[10] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan

[11] Acad Sinica, Genom Res Ctr, Taipei, Taiwan

[12] Kaohsiung Vet Gen Hosp, Dept Surg, Kaohsiung, Taiwan

[13] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan

来源：

BMC GENOMICS | 2013年 / 14卷

关键词：

NONMUSCLE MYOSIN IIA; MICRORNA DYSREGULATION; REGULATORY MODULES; DOWN-REGULATION; TARGET; IDENTIFICATION; COLON; HYPERMETHYLATION; IMPACT;

D O I：

10.1186/1471-2164-14-S5-S12

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：10

共 49 条

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