MicroRNA-543 suppresses colorectal cancer growth and metastasis by targeting KRAS, MTA1 and HMGA2

Oncotarget. 2016 Apr 19;7(16):21825-39. doi: 10.18632/oncotarget.7989.

Abstract

miR-543 has been implicated as having a critical role in the development of breast cancer, endometrial cancer and hepatocellular carcinoma. However, the exact clinical significance and biological functions of miR-543 in colorectal cancer (CRC) remain unclear. Here, we found that miR-543 expression significantly downregulated in tumors from patients with CRC, APCMin mice and a mouse model of colitis-associated colon cancer. miR-543 level was inversely correlated with the metastatic status of patients with CRC and the metastatic potential of CRC cell lines. Moreover, ectopic expression of miR-543 inhibited the proliferation and metastasis of CRC cells in vitro and in vivo by targeting KRAS, MTA1 and HMGA2. Conversely, miR-543 knockdown promoted the proliferation, migration and invasion of CRC cells in vitro and augmented tumor growth and metastasis in vivo. Furthermore, we found that miR-543 expression was negatively correlated with the levels of KRAS, MTA1 and HMGA2 in clinical samples. Collectively, these data show that miR-543 inhibits the proliferation and metastasis of CRC cells by targeting KRAS, MTA1 and HMGA2. Our study highlights a pivotal role for miR-543 as a suppressor in the regulation of CRC growth and metastasis and suggests that miR-543 may serve as a novel diagnostic and prognostic biomarker for CRC metastasis.

Keywords: colorectal cancer; metastasis; miR-543; microRNA; proliferation.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Caco-2 Cells
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • HEK293 Cells
  • HMGA2 Protein / genetics*
  • HMGA2 Protein / metabolism
  • HT29 Cells
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Trans-Activators
  • Transplantation, Heterologous
  • Tumor Burden / drug effects
  • Tumor Burden / genetics

Substances

  • 3' Untranslated Regions
  • HMGA2 Protein
  • KRAS protein, human
  • MIRN544 microRNA, human
  • MicroRNAs
  • MTA1 protein, human
  • Repressor Proteins
  • Trans-Activators
  • Histone Deacetylases
  • Proto-Oncogene Proteins p21(ras)