MicroRNA-203 inhibits tumour growth and metastasis through PDPN

Clin Otolaryngol. 2017 Jun;42(3):620-628. doi: 10.1111/coa.12785. Epub 2016 Nov 8.

Abstract

Objective: MicroRNAs play an important role in regulating hypopharyngeal cancer development. miR-203 has been previously shown to possess antitumour capabilities in many cancers, but not in hypopharyngeal cancer.

Design: Using human normal and hypopharyngeal cancer specimens, we explored the expression levels of miR-203 in the two groups and further correlated them with different stages of cancer and lymph node metastasis.

Setting and participants: Applying human pharynx FaDu cancer cells and lentiviral transduction technique, we investigated the effects of miR-203 on cancer cell viability, migration and invasion. Moreover, we studied the novel relationship between miR-203 and podoplanin (PDPN) in hypopharyngeal cancer.

Results: The downregulated levels of miR-203 in human hypopharyngeal cancer tissues were associated with advanced cancer stages and lymph node metastasis. High levels of miR-203 inhibited cell viability, migration and invasion of hypopharyngeal cancer cells. Further studies suggested miR-203 directly targeted and inhibited PDPN expression. PDPN silencing suppresses hypopharyngeal cancer cell abilities. In addition, PDPN overexpression was able to reverse miR-203 inhibitory effects on cell viability, migration and invasion.

Conclusion: PDPN acts as an oncogene to promote hypopharyngeal cancer cell viability, migration and invasion. miR-203 directly targets PDPN to suppress its expression, thus exerting inhibitory effects on cancer metastasis.

MeSH terms

  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary
  • Cell Movement
  • Cell Survival
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypopharyngeal Neoplasms / genetics*
  • Hypopharyngeal Neoplasms / metabolism
  • Hypopharyngeal Neoplasms / pathology
  • Lymphatic Metastasis
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Neoplasm / genetics*
  • Real-Time Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • MIRN203 microRNA, human
  • Membrane Glycoproteins
  • MicroRNAs
  • PDPN protein, human
  • RNA, Neoplasm