Effects of small interfering RNAs targeting Fascin on gene expression in oral cancer cells.
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.
Chen
Su-Feng
SF
Department of Dental Hygiene, China Medical University, Taichung, Taiwan.
Lin
Chi-Yu
CY
Chang
Yun-Ching
YC
Li
Jhy-Wei
JW
Fu
Earl
E
Chang
Fei-Ni
FN
Lin
Yu-Lu
YL
Nieh
Shin
S
D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015536:Down-Regulation; D004847:Epithelial Cells / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008648:Mesoderm / Q000473:pathology; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics*; D034741:RNA, Small Interfering / Q000502:physiology; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000096:biosynthesis; D051176:beta Catenin / Q000096:biosynthesis
D015820:Cadherins; D002352:Carrier Proteins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D051879:Twist-Related Protein 1; D051176:beta Catenin; C020324:fascin