The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis
- 24 March 2015
- Vol. 65 (6), 977-989
- https://doi.org/10.1136/gutjnl-2015-309372
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, pConclusions MiR-224 promotes CRC metastasis, at least in part, through the regulation of SMAD4. MiR-224 expression in primary CRC, alone or combined with its targets, may have prognostic value for survival of patients with CRC.Keywords
This publication has 33 references indexed in Scilit:
- miR-224 overexpression is a strong and independent prognosticator of short-term relapse and poor overall survival in colorectal adenocarcinomaInternational Journal of Oncology, 2014
- Up-regulation of miR-224 promotes cancer cell proliferation and invasion and predicts relapse of colorectal cancerCancer Cell International, 2013
- Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7gRadiotherapy and Oncology, 2013
- Treatment of HCV Infection by Targeting MicroRNANew England Journal of Medicine, 2013
- Integrated Analysis of Molecular and Clinical Prognostic Factors in Stage II/III Colon CancerJNCI Journal of the National Cancer Institute, 2012
- Comprehensive molecular characterization of human colon and rectal cancerNature, 2012
- Pleiotropic Action of Renal Cell Carcinoma-Dysregulated miRNAs on Hypoxia-Related Signaling PathwaysThe American Journal of Pathology, 2012
- Underexpression of miR-224 in methotrexate resistant human colon cancer cellsBiochemical Pharmacology, 2011
- MicroRNAs: small RNAs with a big role in gene regulationNature Reviews Genetics, 2004
- A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer.1998