Effects of small interfering RNAs targeting Fascin on gene expression in oral cancer cells

J Oral Pathol Med. 2009 Oct;38(9):722-30. doi: 10.1111/j.1600-0714.2009.00769.x. Epub 2009 Apr 15.

Abstract

Background: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. The prognosis of OSCC is usually poor because of extensive local invasion at initial diagnosis. In the literature, Fascin has been reported responsible for cell motility and over-expression of Fascin contributes to an unfavorable clinical course. Nevertheless, the roles of Fascin protein playing in aggressiveness of OSCC and their potential mechanisms need to be elucidated.

Methods: Two cell lines of OSCC (OECM-1 and SCC-25) via the vector-based small interfering RNA (siRNA) to suppress the expression of the Fascin gene were used. Subsequent analyses and observation regarding the expression of Fascin protein and cyto-morphological alterations were detected by Western blot and immunofluorescent microscopy. Boyden chamber invasion assay, cell migration assay and adhesion assay were also applied to investigate the functional changes of OSCC.

Results: There were statistically significant differences (P < 0.05) of Fascin expression before and after silencing. Down-regulation of Fascin protein directly led to changes of cell surface protrusions under immunofluorescent microscopy and resulted in suppression of migration, invasion and increase of adhesion in both cell lines (P < 0.05). Furthermore, down-regulation of Fascin expression also resulted in alterations of E-cadherin, beta-catenin and TWIST at certain level, implicative of an association with epithelial-mesenchymal transition (EMT).

Conclusions: Our results suggest that expression of Fascin protein may play an essential role in regulation of progression of OSCC and contributes to the event of EMT in the early aggressiveness of OSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cadherins / biosynthesis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Migration Assays
  • Cell Transformation, Neoplastic / genetics
  • Down-Regulation
  • Epithelial Cells / pathology
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Mesoderm / pathology
  • Microfilament Proteins / biosynthesis
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / physiology*
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism
  • Neoplasm Invasiveness / genetics*
  • RNA, Small Interfering / physiology
  • Transfection
  • Twist-Related Protein 1 / biosynthesis
  • beta Catenin / biosynthesis

Substances

  • Cadherins
  • Carrier Proteins
  • Microfilament Proteins
  • RNA, Small Interfering
  • Twist-Related Protein 1
  • beta Catenin
  • fascin