MicroRNA-146a promote cell migration and invasion in human colorectal cancer via carboxypeptidase M/src-FAK pathway

Oncotarget. 2017 Apr 4;8(14):22674-22684. doi: 10.18632/oncotarget.15158.

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide, and microRNAs play important roles in CRC progression. This study aimed to investigate the roles of miR-146a-5p in human CRC and their molecular mechanisms. First, we found that miR-146a-5p was significantly upregulated in CRC tissues and promoted the migration of CRC cells. Then, we identified carboxypeptidase M (CPM) as a direct target of miR-146a-5p, and found that it inhibited the migration and invasion of CRC cells. Our results also showed that CPM expression was positively correlated with overall survival and negatively correlated with recurrence, lymph node invasion, and N stage. Furthermore, we demonstrated that both miR-146a-5p and CPM regulated Src and FAK expression, while the Src-FAK signaling pathway is widely known to be associated with the migration and invasion of multiple tumor cells. This study is the first to demonstrate the functional and mechanistic relationship of the miR-146a-5p/CPM/Src-FAK axis and its effect on the migration and invasion of CRC cells. Thus, miR-146a-5p represents potential targets for CRC diagnosis and therapy.

Keywords: carboxypeptidase M; colorectal cancer; invasion; miR-146a-5p; migration.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Movement*
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Signal Transduction
  • Survival Rate
  • Tumor Cells, Cultured
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism

Substances

  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • MIRN146 microRNA, human
  • MicroRNAs
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • src-Family Kinases
  • carboxypeptidase M
  • Metalloendopeptidases