Small interfering RNA-mediated downregulation of beta-catenin inhibits invasion and migration of colon cancer cells in vitro
Jianjun Han, Binbin Gao, Xing Jin, Zhongfa Xu, Zengjun Li, Yanlai Sun, Bao Song
Med Sci Monit 2012; 18(7): BR273-280
Available online: 2012-06-28
Background: Abnormal regulation of Wnt/beta-catenin signaling and subsequently increased beta-catenin expression have been found to be involved in the proliferation and growth of colon cancer cells. Whether the down-regulation of beta-catenin in colon cancer may result in compromised invasion and migration in vitro still remains to be determined.
Material/Methods: A human colon cancer cell line (LoVo cells) was transfected with small interfering RNA (siRNA) targeting beta-catenin. RT-PCR, Western blot assay, flow cytometry, cell adhesion assay, scratch wound assay, and matrigel invasion assay were performed, and the correlation between cell invasion and migration and beta-catenin expressions was analyzed.
Results: siRNA-mediated down-regulation of beta-catenin elevated the E-cadherin expression but reduced the MMP-7 and CD44v6 expressions, which increased the adhesion between LoVo cells but decreased the adhesion of LoVo cells to fibronectin. Significant inhibition of cell invasion and migration was also observed following RNA interference with beta-catenin siRNA.
Conclusions: siRNA-mediated downregulation of beta-catenin could be valuable for defining gene expression and functional programs downstream of oncogenic beta-catenin signals, which, in turn, may be helpful to isolate novel diagnostic markers, and for designing tumor-specific intervention at downstream targets of oncogenic beta-catenin.
Keywords: Neoplasm Invasiveness, RNA, Messenger - metabolism, Matrix Metalloproteinase 7 - metabolism, Gene Expression Regulation, Neoplastic, Down-Regulation - genetics, Colonic Neoplasms - pathology, Cell Movement - genetics, Cell Line, Tumor, Cell Adhesion, Cadherins - metabolism, Antigens, CD44 - metabolism, RNA, Small Interfering - metabolism, Transfection, beta Catenin - metabolism