MiR-199a inhibits the ability of proliferation and migration by regulating CD44-Ezrin signaling in cutaneous squamous cell carcinoma cells

Int J Clin Exp Pathol. 2014 Sep 15;7(10):7131-41. eCollection 2014.

Abstract

Cutaneous squamous cell carcinoma (cSCC), the second most common form of human cancer, is an epithelial skin tumor, which can result in metastasis with lethal consequences accounting for about 20% of all skin cancer-related deaths. The metastasis is the main reason for cSCC-related deaths with an overall 5-year survival rate < 30% in cases that spread systemically. The role of miRNAs has been involved in SCC of different origins. Recent data have revealed that the expression of miRNA-199a was changed in many human cancers. In this study, we found that miR-199a was significantly decreased in cSCC tissues, which had an inverse relationship with CD44. MiR-199a specifically regulated the expression of CD44 at mRNA and protein levels, and the interaction between CD44 and Ezrin in cSCC cells. Moreover, the suppressive role of miR-199a in cell migration in cSCC cells was also associated with the activity of MMP2 and MMP9. Taken together, our data indicated that increased expression of endogenous mature miR-199a might prevent the growth and migration of human cSCC via decreasing the expression of CD44 and regulating the interaction between CD44 and Ezrin, which may provide a potentially important therapeutic target for human cSCC.

Keywords: CD44; Cutaneous squamous cell carcinoma; Ezrin; MMP2; MMP9; miR-199a.

MeSH terms

  • 3' Untranslated Regions
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Time Factors
  • Transfection

Substances

  • 3' Untranslated Regions
  • CD44 protein, human
  • Cytoskeletal Proteins
  • Hyaluronan Receptors
  • MicroRNAs
  • RNA, Messenger
  • ezrin
  • mirn199 microRNA, human
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9