ARID1A regulates E-cadherin expression in colorectal cancer cells: a promising candidate therapeutic target

Background Metastasis is a major cause of death in Colorectal cancer (CRC) patients, and the Epithelial-mesenchymal transition (EMT) has been known to be a crucial event in cancer metastasis. Downregulated expression of AT-rich interaction domain-containing protein 1A (ARID1A), a bona fide tumor suppressor gene, plays an important role in promoting EMT and CRC metastasis, but the underlying molecular mechanisms remain poorly understood. Here, we evaluated the impact of ARID1A knockdown and overexpression on the expression of EMT-related genes, E-cadherin and beta-catenin, in human CRC cells. Methods and results The expression levels of ARID1A, E-cadherin and beta-catenin in CRC cell lines were detected via real-time quantitative PCR (qPCR) and western blot. ARID1A overexpression and shRNA-mediated knockdown were performed to indicate the effect of ARID1A expression on E-cadherin and beta-catenin expression in CRC cell lines. The effect of ARID1A knockdown on the migration ability of HCT116 cells was assessed using wound-healing assay. We found that the mRNA and protein expression of adhesive protein E-cadherin was remarkably downregulated in response to shRNA-mediated ARID1A knockdown in HCT116 and HT29 cells. Conversely, overexpression of ARID1A in SW48 cells significantly increased E-cadherin expression. In addition, ARID1A silencing promoted the migration of HCT116 cells. ARID1A knockdown and overexpression did not alter the level of beta-catenin expression. Conclusions Our study demonstrates that E-cadherin levels were closely correlated with ARID1A expression. Thus, ARID1A downregulation may promote CRC metastasis through decreasing EMT-related protein E-cadherin and promoting epithelial cell movement. ARID1A could represent a promising candidate therapeutic target for CRC.