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

Int J Oncol. 2017 Feb;50(2):487-496. doi: 10.3892/ijo.2016.3813. Epub 2016 Dec 20.

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.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Blotting, Western
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / biosynthesis*
  • Proto-Oncogene Proteins p21(ras) / genetics

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • MIRN487 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins p21(ras)