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

• Published in: International Journal of Oncology Vol. 50; no. 2; pp. 487 - 496
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.02.2017; Spandidos Publications UK Ltd
• Subjects: Biomarkers, Tumor; Biomarkers, Tumor - genetics; Blotting, Western; Care and treatment; Colorectal cancer; Colorectal Neoplasms; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Development and progression; Gene expression; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Neoplastic - genetics; Genetic aspects; Health aspects; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Liver Neoplasms - genetics; Liver Neoplasms - mortality; Liver Neoplasms - secondary; Lung cancer; Lymphatic system; Medical prognosis; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - genetics; Multivariate analysis; Neoplasm Invasiveness; Neoplasm Invasiveness - genetics; Oligonucleotide Array Sequence Analysis; Patients; Polymerase Chain Reaction; Prognosis; Proto-Oncogene Proteins p21(ras); Proto-Oncogene Proteins p21(ras) - biosynthesis; Proto-Oncogene Proteins p21(ras) - genetics; Studies; Tumors; United States > US
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2016.3813

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.