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Role of miR-143 targeting KRAS in colorectal tumorigenesis

Oncogene volume 28, pages 1385–1392 (2009)Cite this article

Abstract

Dysregulated expression of microRNAs (miRNAs) is associated with a variety of diseases, including colorectal cancer. By comparing more than 200 miRNAs in 13 pairs of matched colorectal cancer and normal adjacent tissue samples through qRT-PCR and microarray analysis, we found a widespread disruption of miRNA expression during colorectal tumorigenesis. In particular, among a panel of presumed targets generated by in silico analysis that may interact with these aberrantly expressed miRNAs, KRAS oncogene has been further experimentally validated as the target of miR-143. First, an inverse correlation between KRAS protein and miR-143 in vivo was found. Second, KRAS expression in Lovo cells was significantly abolished by treatment with miR-143 mimic, whereas miR-143 inhibitor increased KRAS protein level. Third, luciferase reporter assay confirmed that miR-143 directly recognize the 3′-untranslated region of KRAS transcripts. Four, Lovo cells treated with miR-143 inhibitor showed a stimulated cell proliferation, whereas miR-143 overexpression had an opposite effect. Finally, inhibition of KRAS expression by miR-143 inhibits constitutive phosphorylation of ERK1/2. Taken together, the present study provides the first evidences that miR-143 is significant in suppressing colorectal cancer cell growth through inhibition of KRAS translation.

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Acknowledgements

We thank Yun Luo for pathological diagnosis and sample collection. This work was supported by National Natural Science Foundation of China (nos. 30225037, 30471991 and 30570731); 973 Program of China (nos. 2006CB503909 and 2004CB518603) and Natural Science Foundation of Jiangsu province (nos. BK2004082 and BK2006714).

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Author notes

  1. X Chen, X Guo, H Zhang and Y Xiang: These authors contributed equally to this work.

Authors and Affiliations

  1. Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China

    X Chen, X Guo, H Zhang, Y Xiang, J Chen, Y Yin, X Cai, K Wang, G Wang, L Zhu, J Wang, R Yang, Y Zhang, Z Ren, K Zen, J Zhang & C-Y Zhang

  2. Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

    H Zhang

  3. Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Y Ba

  4. Jiangsu CDC–Nanjing University Joint Institute of Virology, Nanjing, Jiangsu, China

    K Zen

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Correspondence to K Zen, J Zhang or C-Y Zhang.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Chen, X., Guo, X., Zhang, H. et al. Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene 28, 1385–1392 (2009). https://doi.org/10.1038/onc.2008.474

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