c-MYC-regulated miR-23a/24-2/27a cluster promotes mammary carcinoma cell invasion and hepatic metastasis by targeting Sprouty2

J Biol Chem. 2013 Jun 21;288(25):18121-33. doi: 10.1074/jbc.M113.478560. Epub 2013 May 6.


Emerging evidence indicates that the miR-23a/24-2/27a cluster may possess a causal role in mammary tumorigenesis and function as a novel class of oncogenes. However, the regulatory mechanism of the miR-23a/24-2/27a cluster in mammary carcinoma cell invasion and migration is still largely unknown. We observed that the expression levels of miR-23a, miR-24-2 and miR-27a were significantly higher in breast cancer with lymph node metastasis, compared with that from patients without lymph node metastasis or normal tissue. Forced expression of the miR-23a/24-2/27a cluster promoted mammary carcinoma cell migration, invasion, and hepatic metastasis, through targeting Sprouty2 (SPRY2) and consequent activation of p44/42 MAPK. Epidermal growth factor induced the expression of the transcription factor c-MYC, which promoted the expression of mature miR-23a, miR-24-2, and miR-27a and subsequently decreased expression of SPRY2 and activated p44/42 MAPK to promote mammary carcinoma cell migration and invasion. We therefore suggest a novel link between epidermal growth factor and the miR-23a/24-2/27a cluster via the regulation of c-MYC, providing the potential for the miR-23a/24-2/27a cluster to be used as biomarker in the diagnosis and/or treatment of breast cancer.

Keywords: Breast Cancer; Epidermal Growth Factor (EGF); Metastasis; MicroRNA; Myc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Movement / genetics
  • Epidermal Growth Factor / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary
  • MCF-7 Cells
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinases / metabolism
  • Mutation
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-myc / genetics*
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Heterologous


  • Intracellular Signaling Peptides and Proteins
  • MIRN23a microRNA, human
  • MIRN24 microRNA, human
  • MIRN27 microRNA, human
  • MYC protein, human
  • Membrane Proteins
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • SPRY2 protein, human
  • Epidermal Growth Factor
  • Mitogen-Activated Protein Kinases