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

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

研究成果: Contribution to journalArticle査読

11 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)487-496
ページ数10
ジャーナルInternational journal of oncology
50
2
DOI
出版ステータス出版済み - 2 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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