MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1
Open Access
- 23 August 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in Protein & Cell
- Vol. 5 (11), 851-861
- https://doi.org/10.1007/s13238-014-0093-5
Abstract
MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.Keywords
This publication has 45 references indexed in Scilit:
- Tumor-Suppressive Function of miR-139-5p in Esophageal Squamous Cell CarcinomaPLOS ONE, 2013
- MiR-139 inhibits invasion and metastasis of colorectal cancer by targeting the type I insulin-like growth factor receptorBiochemical Pharmacology, 2012
- Nanoparticle-based delivery of siDCAMKL-1 increases microRNA-144 and inhibits colorectal cancer tumor growth via a Notch-1 dependent mechanismJournal of Nanobiotechnology, 2011
- The MicroRNA miR-139 Suppresses Metastasis and Progression of Hepatocellular Carcinoma by Down-regulating Rho-Kinase 2Gastroenterology, 2011
- Autocrine Motility Factor Receptor Signaling Pathway Promotes Cell Invasion via Activation of ROCK-2 in Esophageal Squamous Cell Cancer CellsCancer Investigation, 2010
- Metastamir: The Field of Metastasis-Regulatory microRNA Is SpreadingCancer Research, 2009
- Up-regulation of miR-200 and let-7 by Natural Agents Leads to the Reversal of Epithelial-to-Mesenchymal Transition in Gemcitabine-Resistant Pancreatic Cancer CellsCancer Research, 2009
- Oncomirs — microRNAs with a role in cancerNature Reviews Cancer, 2006
- MicroRNAs: Genomics, Biogenesis, Mechanism, and FunctionCell, 2004
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001