Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration and invasion and is directly regulated by tumor-suppressive microRNA-133a in head and neck squamous cell carcinoma

Int J Oncol. 2012 Jun;40(6):1770-8. doi: 10.3892/ijo.2012.1390. Epub 2012 Feb 29.


Our expression signatures of human cancers including head and neck squamous cell carcinoma (HNSCC) demonstrated that downregulation of microRNA-133a (miR-133a) were frequently observed in cancer cells. The restoration of miR-133a in cancer cells revealed that it functions as a tumor suppressor. In this study, we investigated the novel molecular targets of miR-133a in HNSCC cancer cells and its oncogenic function, especially as it contributes to cancer cell migration and invasion. The genome-wide gene expression analysis and bioinformatics study showed that actin-related protein 2/3 complex subunit 5 (ARPC5) is a candidate target of miR-133a. Furthermore, luciferase reporter assay demonstrated that ARPC5 is directly regulated by miR-133a. Silencing of ARPC5 revealed significant inhibition of cell migration and invasion in HNSCC cell lines, SAS, HSC3 and IMC-3. In HSC3 cells, restoration of miR-133a or silencing ARPC5 led to a reorganization of the actin cytoskeleton and a subsequent change in cell morphology to a round, bleb-like shape. The expression levels of ARPC5 were significantly higher in HNSCC tissues than in non-cancer tissues. Immunohistochemistry showed that the levels of ARPC5 expression were significantly higher in invasive cancer cells. ARPC5 contributed to cancer cell migration and invasion in HNSCC and this gene was directly regulated by miR-133a. Our analysis of novel tumor-suppressive miR‑133a-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Binding Sites
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • RNA Interference


  • 3' Untranslated Regions
  • ARPC5 protein, human
  • Actin-Related Protein 2-3 Complex
  • MIRN133 microRNA, human
  • MicroRNAs