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Comprehensive gene and microRNA expression profiling reveals the crucial role of hsa-let-7i and its target genes in colorectal cancer metastasis

Molecular Biology Reports volume 39, pages 1471–1478 (2012)Cite this article

Abstract

Accumulating evidence has demonstrated that miRNAs play important roles in the occurrence and development of colorectal cancer (CRC). However, whether miRNAs are associated with the metastasis of CRC remains largely unexplored. The aim of the current study is to profile miRNAs in different CRC metastatic cell lines to identify the biomarkers in CRC metastasis. Gene and miRNA expression profiling was performed to analyze the global expression of mRNAs and miRNAs in the four human CRC cell lines (LoVo, SW480, HT29 and Caco-2) with different potential of metastasis. Expression patterns of mRNAs and miRNAs were altered in different CRC cell lines. By developing an integrated bioinformatics analysis of gene and miRNA expression patterns, hsa-let-7i was identified to show the highest degree in the microRNA-GO-network and microRNA-Gene-network. The expression level of hsa-let-7i was further validated by qRT-PCR in CRC cells. In addition, the targets of hsa-let-7i were predicted by two programs TargetScan and PicTar, and target genes were validated by expression profiling in the most epresentative LoVo and Caco-2 cell lines. Eight genes including TRIM41, SOX13, SLC25A4, SEMA4F, RPUSD2, PLEKHG6, CCND2, and BTBD3 were identified as hsa-let-7i targets. Our data showed the power of comprehensive gene and miRNA expression profiling and the application of bioinformatics tools in the identification of novel biomarkers in CRC metastasis.

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Acknowledgments

This work was supported by the National 973 Basic Research Program of China (No. 2008CB517403), the Grants from Shanghai Science and Technology Development Fund (No. 09JC1411600), the National 863 High Technology Foundation (No. 2009AA02Z118), and Doctoral Fund of Shanghai Jiao Tong University (No. BXJ201039).

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The authors declare that they have no conflict of interests.

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Affiliations

  1. Department of Surgery, The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, 600 Yishan Road, Shanghai, 200233, People’s Republic of China

    Peng Zhang, Yanlei Ma, Feng Wang, Jianjun Yang, Zhihua Liu, Jiayuan Peng & Huanlong Qin

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  1. Peng Zhang
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  2. Yanlei Ma
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  3. Feng Wang
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Correspondence to Huanlong Qin.

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Peng Zhang, Yanlei Ma, and Feng Wang have equally contributed to this paper.

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Fig. 1S

Pathway analysis based on miRNA target genes. Significant pathways targeted by upregulated miRNA were shown. The vertical axis was the pathway category, and the horizontal axis was the enrichment of pathways. (JPEG 182 kb)

Fig. 2S

MiRNA-Gene-network analysis. Red box nodes represented miRNA, blue cycle nodes represented mRNA, and edges showed the inhibitory effect of miRNA on mRNA. Upregulated and downregulated miRNAs had separate and specific targets. The five key miRNAs in the network were hsa-miR-130a, hsa-let-7i, hsa-miR-106b, hsa-let-7g, and hsa-miR-15b. (JPEG 752 kb)

Fig. 3S

MiRNA-GO-network analysis. The circle represented gene, the square represented miRNA, and their relationship was represented by one edge. The degree represented the contribution of individual miRNA or gene to the genes or miRNAs around. The six key miRNAs in the network were hsa-miR-371-3p, hsa-let-7i, hsa-let-7g, hsa-miR-15b, hsa-miR-199a-3p, and hsa-miR-26b. (JPEG 475 kb)

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Zhang, P., Ma, Y., Wang, F. et al. Comprehensive gene and microRNA expression profiling reveals the crucial role of hsa-let-7i and its target genes in colorectal cancer metastasis. Mol Biol Rep 39, 1471–1478 (2012). https://doi.org/10.1007/s11033-011-0884-1

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  • DOI: https://doi.org/10.1007/s11033-011-0884-1

Keywords

  • Colorectal cancer
  • Bioinformatics
  • hsa-let-7i
  • Metastasis