Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 50, Issue 2, Pages 487-496Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3813
Keywords
miR-487b; colorectal cancer; liver metastasis; KRAS; LRP6
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Funding
- [21390360]
- [30322184]
- [24390315]
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Recent studies have shown that microRNAs (miRNAs) are involved in the progression of colorectal cancer (CRC). The aim of this study is to identify a novel miRNA that especially relates to liver metastasis and to explore the underlying mechanism. Differentially expressed miRNAs were analyzed using microarray, in primary CRC tumors without metastasis (n=16), those with liver metastasis (n=12), and liver metastatic lesions (n=8). We found that miR-487b level decreased in liver metastatic lesions, and qRT-PCR confirmed the results in the validating cohort (n=134). Survival analysis indicated that high expression of miR-487b was associated with better prognosis. In vitro studies were also performed to investigate the functional significance of miR-487b in human CRC cell lines. miR-487b showed an inhibitory effect on cell proliferation and invasion of CRC cells. miR-487b downregulated KRAS and inhibited its downstream signal pathways, and the luciferase reporter assay revealed that miR-487b directly targeted LRP6, a receptor for WNT/beta-catenin signaling. These findings showed that decrease in miR-487b was related with liver metastasis. Our data suggest a possibility that miR-487b may suppress metastasis of CRC progression through inhibition of KRAS.
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