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 Liu; Krishna 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

doi:10.1136/gutjnl-2015-309372

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

Research output: Contribution to journal › Article

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 language	English
Journal	Gut
DOIs	https://doi.org/10.1136/gutjnl-2015-309372
Publication status	Accepted/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

The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis. / Ling, Hui; Pickard, Karen; Ivan, Cristina; Isella, Claudio; Ikuo, Mariko; Mitter, Richard; Spizzo, Riccardo; Bullock, Marc D.; Braicu, Cornelia; Pileczki, Valentina; Vincent, Kimberly; Pichler, Martin; Stiegelbauer, Verena; Hoefler, Gerald; Almeida, Maria I.; Hsiao, Annie; Zhang, Xinna; Primrose, John N.; Packham, Graham K.; Liu, Kevin; Bojja, Krishna; Gafà, Roberta; Xiao, Lianchun; Rossi, Simona; Song, Jian H.; Vannini, Ivan ; Fanini, Francesca; Kopetz, Scott; Zweidler-McKay, Patrick; Wang, Xuemei; Ionescu, Calin; Irimie, Alexandru; Fabbri, Muller; Lanza, Giovanni; Hamilton, Stanley R.; Berindan-Neagoe, Ioana; Medico, Enzo; Mirnezami, Alex H.; Calin, George A.; Nicoloso, Milena S.

In: Gut, 24.03.2015.

Research output: Contribution to journal › Article

Ling, H, Pickard, K, Ivan, C, Isella, C, Ikuo, M, Mitter, R, Spizzo, R, Bullock, MD, Braicu, C, Pileczki, V, Vincent, K, Pichler, M, Stiegelbauer, V, Hoefler, G, Almeida, MI, Hsiao, A, Zhang, X, Primrose, JN, Packham, GK, Liu, K, Bojja, K, Gafà, R, Xiao, L, Rossi, S, Song, JH, Vannini, I , Fanini, F, Kopetz, S, Zweidler-McKay, P, Wang, X, Ionescu, C, Irimie, A, Fabbri, M, Lanza, G, Hamilton, SR, Berindan-Neagoe, I, Medico, E, Mirnezami, AH, Calin, GA & Nicoloso, MS 2015, 'The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis', Gut. https://doi.org/10.1136/gutjnl-2015-309372

Ling, Hui ; Pickard, Karen ; Ivan, Cristina ; Isella, Claudio ; Ikuo, Mariko ; Mitter, Richard ; Spizzo, Riccardo ; Bullock, Marc D. ; Braicu, Cornelia ; Pileczki, Valentina ; Vincent, Kimberly ; Pichler, Martin ; Stiegelbauer, Verena ; Hoefler, Gerald ; Almeida, Maria I. ; Hsiao, Annie ; Zhang, Xinna ; Primrose, John N. ; Packham, Graham K. ; Liu, Kevin ; Bojja, Krishna ; Gafà, Roberta ; Xiao, Lianchun ; Rossi, Simona ; Song, Jian H. ; Vannini, Ivan ; Fanini, Francesca ; Kopetz, Scott ; Zweidler-McKay, Patrick ; Wang, Xuemei ; Ionescu, Calin ; Irimie, Alexandru ; Fabbri, Muller ; Lanza, Giovanni ; Hamilton, Stanley R. ; Berindan-Neagoe, Ioana ; Medico, Enzo ; Mirnezami, Alex H. ; Calin, George A. ; Nicoloso, Milena S. / The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis. In: Gut. 2015.

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title = "The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis",

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",

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

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T1 - The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis

AU - Ling, Hui

AU - Pickard, Karen

AU - Ivan, Cristina

AU - Isella, Claudio

AU - Ikuo, Mariko

AU - Mitter, Richard

AU - Spizzo, Riccardo

AU - Bullock, Marc D.

AU - Braicu, Cornelia

AU - Pileczki, Valentina

AU - Vincent, Kimberly

AU - Pichler, Martin

AU - Stiegelbauer, Verena

AU - Hoefler, Gerald

AU - Almeida, Maria I.

AU - Hsiao, Annie

AU - Zhang, Xinna

AU - Primrose, John N.

AU - Packham, Graham K.

AU - Liu, Kevin

AU - Bojja, Krishna

AU - Gafà, Roberta

AU - Xiao, Lianchun

AU - Rossi, Simona

AU - Song, Jian H.

AU - Vannini, Ivan

AU - Fanini, Francesca

AU - Kopetz, Scott

AU - Zweidler-McKay, Patrick

AU - Wang, Xuemei

AU - Ionescu, Calin

AU - Irimie, Alexandru

AU - Fabbri, Muller

AU - Lanza, Giovanni

AU - Hamilton, Stanley R.

AU - Berindan-Neagoe, Ioana

AU - Medico, Enzo

AU - Mirnezami, Alex H.

AU - Calin, George A.

AU - Nicoloso, Milena S.

PY - 2015/3/24

Y1 - 2015/3/24

N2 - 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

AB - 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

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10.1136/gutjnl-2015-309372