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/β-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.
All Science Journal Classification (ASJC) codes
- Cancer Research