TY - JOUR
T1 - Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer
AU - Hata, Tsuyoshi
AU - Mokutani, Yukako
AU - Takahashi, Hidekazu
AU - Inoue, Akira
AU - Munakata, Koji
AU - Nagata, Kazuya
AU - Haraguchi, Naotsugu
AU - Nishimura, Junichi
AU - Hata, Taishi
AU - Matsuda, Chu
AU - Murata, Kohei
AU - Mizushima, Tsunekazu
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Yamamoto, Hirofumi
PY - 2017/2
Y1 - 2017/2
N2 - 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.
AB - 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.
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U2 - 10.3892/ijo.2016.3813
DO - 10.3892/ijo.2016.3813
M3 - Article
C2 - 28000854
AN - SCOPUS:85013067864
SN - 1019-6439
VL - 50
SP - 487
EP - 496
JO - International journal of oncology
JF - International journal of oncology
IS - 2
ER -
