Journal
BRITISH JOURNAL OF CANCER
Volume 110, Issue 9, Pages 2300-2309Publisher
SPRINGERNATURE
DOI: 10.1038/bjc.2014.122
Keywords
colorectal cancer; miR-145; Fascin-1; growth; metastasis
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Funding
- Natural Sciences Foundation of China [81071207, 81271622, 31271053]
- 973 Program [2010CB912201, 2010CB529904]
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Background: Recent studies have reported miR-145 dysregulated in colorectal cancer (CRC). In this study, miR-145 profiles were compared between CRC and corresponding non-tumour tissues. Methods: The expression levels of miR-145 were analysed in CRC cell lines and tumour tissues by real-time PCR. A luciferase reporter assay confirmed direct targets. The functional effects of miR-145 were examined in transfected CRC cells in vitro and in vivo using established assays. Results: Downregulation of miR-145 was detected in most primary CRC tumours, and was significantly correlated with a more aggressive phenotype of CRC in patients. In CRC cell lines, ectopic overexpression of miR-145 inhibited cell proliferation, motility and invasion in vitro. Stable overexpression of miR-145 suppressed tumour growth and pulmonary metastasis in vivo. Further studies indicated that miR-145 may directly interact with the 30-untranslated region (30-UTR) of Fascin-1 messenger RNA ( mRNA), downregulating its mRNA and protein expression levels. In clinical specimens, Fascin-1 expression was negatively correlated with miR-145 expression. Conclusions: MiR-145 has a critical role in the inhibition of invasive and metastatic capacities of CRC, probably through directly targeting Fascin-1. This miRNA may be involved in the development and progression of CRC.
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