The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis

Hui Ling, Karen Pickard, Cristina Ivan, Claudio Isella, Mariko Ikuo, Richard Mitter, Riccardo Spizzo, Marc D. Bullock, Cornelia Braicu, Valentina Pileczki, Kimberly Vincent, Martin Pichler, Verena Stiegelbauer, Gerald Hoefler, Maria I. Almeida, Annie Hsiao, Xinna Zhang, John N. Primrose, Graham K. Packham, Kevin LiuKrishna Bojja, Roberta Gafà, Lianchun Xiao, Simona Rossi, Jian H. Song, Ivan Vannini, Francesca Fanini, Scott Kopetz, Patrick Zweidler-McKay, Xuemei Wang, Calin Ionescu, Alexandru Irimie, Muller Fabbri, Giovanni Lanza, Stanley R. Hamilton, Ioana Berindan-Neagoe, Enzo Medico, Alex H. Mirnezami, George A. Calin, Milena S. Nicoloso

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Abstract

Objective MicroRNA (miRNA) expression profile can be used as prognostic marker for human cancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis. Design We performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by quantitative real-time PCR (qRT-PCR). We tested metastatic activity of selected miRNAs and identified miRNA targets by prediction algorithms, qRT-PCR, western blot and luciferase assays. Clinical outcomes were analysed in six sets of CRC cases (n=449), including The Cancer Genome Atlas (TCGA) consortium and correlated with miR-224 status. We used the Kaplan-Meier method and log-rank test to assess the difference in survival between patients with low or high levels of miR-224 expression. Results MiR-224 expression increases consistently with tumour burden and microsatellite stable status, and miR-224 enhances CRC metastasis in vitro and in vivo. We identified SMAD4 as a miR-224 target and observed negative correlation (Spearman Rs=-0.44, p

Original languageEnglish
JournalGut
DOIs
Publication statusAccepted/In press - Mar 24 2015

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ASJC Scopus subject areas

  • Gastroenterology

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Ling, H., Pickard, K., Ivan, C., Isella, C., Ikuo, M., Mitter, R., Spizzo, R., Bullock, M. D., Braicu, C., Pileczki, V., Vincent, K., Pichler, M., Stiegelbauer, V., Hoefler, G., Almeida, M. I., Hsiao, A., Zhang, X., Primrose, J. N., Packham, G. K., ... Nicoloso, M. S. (Accepted/In press). The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis. Gut. https://doi.org/10.1136/gutjnl-2015-309372