Dataset Information

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

ABSTRACT: 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). 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.

SUBMITTER: Chen WS

PROVIDER: S-EPMC3852113 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Chen Wei-Shone WS Chen Ting-Wen TW Yang Tzu-Hsien TH Hu Ling-Yueh LY Pan Hung-Wei HW Leung Chung-Man CM Li Sung-Chou SC Ho Meng-Ru MR Shu Chih-Wen CW Liu Pei-Feng PF Yu Shou-Yu SY Tu Ya-Ting YT Lin Wen-Chang WC Wu Tony T TT Tsai Kuo-Wang KW

BMC genomics 20131016

<h4>Background</h4>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.<h4>Results</h4>The objective of this study was to iden ...[more]

PMID: 24564330

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Project description:BACKGROUND:Colorectal cancer (CRC) is still a leading cause of death worldwide. Recent studies have pointed to an important role of microRNAs in carcinogenesis. Several microRNAs are described as aberrantly expressed in CRC tissues and in the serum of patients. However, functional outcomes of microRNA aberrant expression still need to be explored at the cellular level. Here, we aimed to investigate the effects of microRNAs aberrantly expressed in CRC samples in the proliferation and cell death of a CRC cell line. METHODS:We transfected 31 microRNA mimics into HCT116 cells. Total number of live propidium iodide negative (PI-) and dead (PI+) cells were measured 4?days post-transfection by using a high content screening (HCS) approach. HCS was further used to evaluate apoptosis (via Annexin V and PI staining), and to discern between intrinsic and extrinsic apoptotic pathways, by detecting cleaved Caspase 9 and 8, respectively. To reveal mRNA targets and potentially involved mechanisms, we performed microarray gene expression and functional pathway enrichment analysis. Quantitative PCR and western blot were used to validate potential mRNA targets. RESULTS:Twenty microRNAs altered the proliferation of HCT116 cells in comparison to control. miR-22-3p, miR-24-3p, and miR-101-3p significantly repressed cell proliferation and induced cell death. Interestingly, all anti-proliferative microRNAs in our study had been previously described as poorly expressed in the CRC samples. Predicted miR-101-3p targets that were also downregulated by in our microarray were enriched for genes associated with Wnt and cancer pathways, including MCL-1, a member of the BCL-2 family, involved in apoptosis. Interestingly, miR-101-3p preferentially downregulated the long anti-apoptotic MCL-1?L isoform, and reduced cell survival specifically by activating the intrinsic apoptosis pathway. Moreover, miR-101-3p also downregulated IL6ST, STAT3A/B, and MYC mRNA levels, genes associated with stemness properties of CRC cells. CONCLUSIONS:microRNAs upregulated in CRC tend to induce proliferation in vitro, whereas microRNAs poorly expressed in CRC halt proliferation and induce cell death. We provide novel evidence linking preferential inhibition of the anti-apoptotic MCL-1?L isoform by miR-101-3p and consequent activation of the intrinsic apoptotic pathway as potential mechanisms for its antitumoral activity, likely due to the inhibition of the IL-6/JAK/STAT signaling pathway.

Dataset Information

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

Publications

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

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