Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

Hata,Tsuyoshi; Mokutani,Yukako; Takahashi,Hidekazu; Inoue,Akira; Munakata,Koji; Nagata,Kazuya; Haraguchi,Naotsugu; Nishimura,Junichi; Hata,Taishi; Matsuda,Chu; Murata,Kohei; Mizushima,Tsunekazu; Doki,Yuichiro; Mori,Masaki; Yamamoto,Hirofumi

doi:10.3892/ijo.2016.3813

Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

Authors:
- Tsuyoshi Hata
- Yukako Mokutani
- Hidekazu Takahashi
- Akira Inoue
- Koji Munakata
- Kazuya Nagata
- Naotsugu Haraguchi
- Junichi Nishimura
- Taishi Hata
- Chu Matsuda
- Kohei Murata
- Tsunekazu Mizushima
- Yuichiro Doki
- Masaki Mori
- Hirofumi Yamamoto
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Affiliations: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan, Department of Surgery, Yao Municipal Hospital, Yao, Osaka 581-0069, Japan, Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan, Department of Surgery, Suita Municipal Hospital, Suita, Osaka 564-0082, Japan
Published online on: December 20, 2016 https://doi.org/10.3892/ijo.2016.3813
Pages: 487-496

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Abstract

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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