miR-136 suppresses tumor invasion and metastasis by targeting RASAL2 in triple-negative breast cancer

Oncol Rep. 2016 Jul;36(1):65-71. doi: 10.3892/or.2016.4767. Epub 2016 Apr 25.

Abstract

MicroRNAs play an important role in the regulation of cancer migration, invasion and metastasis. Patients with triple-negative breast cancer (TNBC) have a high incidence of early relapse and metastasis; however, the molecular basis for metastasis and recurrence in these individuals remains largely unknown. Herein, we demonstrate that miR-136 is an anti-invasive microRNA in TNBC and suppresses mesenchymal invasion and metastasis. Our results demonstrated that miR-136 was downregulated in TNBC and negative correlated with the WHO grades. However, RASAL2 was identified as a functional target of miR-136, and was overexpressed in TNBC and correlates with pathological grades. Moreover, overexpression of RASAL2 in a breast cancer cell line rescued miR-136-mediated cell migration and invasion. In conclusion, these results indicate that the miR-136/RASAL2/MET axis act as a suppressor of TNBC metastasis.

MeSH terms

  • Animals
  • Cadherins / biosynthesis
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • GTPase-Activating Proteins
  • Genes, Tumor Suppressor
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / genetics
  • Snail Family Transcription Factors / biosynthesis
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology*
  • Vimentin / biosynthesis

Substances

  • Cadherins
  • Carrier Proteins
  • GTPase-Activating Proteins
  • MIRN136 microRNA, human
  • MicroRNAs
  • RASAL2 protein, human
  • Snail Family Transcription Factors
  • Vimentin