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

Abstract

Background Metastasis is a major cause of death in colorectal cancer (CRC) patients, and the epithelialmesenchymal 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 de 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 β-catenin, in human CRC cells. Methods and ResultsThe expression levels of ARID1A, E-cadherin and β-catenin in CRC cell lines were detected via real-time quantitative PCR (qPCR) and western blot. ARID1A overexpression and shRNAmediated knockdown were performed to indicate the effect of ARID1A expression on E-cadherin and βcatenin 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 signi cantly increased E-cadherin expression. In addition, ARID1A silencing promoted the migration of HCT116 cells. ARID1A knockdown and overexpression did not alter the level of β-catenin expression. ConclusionOur 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.

Liposomal DQ in Combination with Copper Inhibits ARID1A Mutant Ovarian Cancer Growth

“…E-cadherin expression was downregulated in the ARID1A mutation cell line. The decreased E-cadherin increased cell motility and promoted tumor metastasis [44]. We found the absence of ARID1A decreased E-cadherin and elevated N-cadherin and Vimentin (Figure 3D,E).…”

“…The cold microenvironment indicated a decrease in tumor-inhibitory factors but an increase in tumor-promoting factors [44]. Tumor necrosis factor-α (TNFα) was a positive factor in the cancer microenvironment showing anti-cancer efficacy [45].…”

Comprehensive Analysis of Subtype-Specific Molecular Characteristics of Colon Cancer: Specific Genes, Driver Genes, Signaling Pathways, and Immunotherapy Responses

“…ARID1A is essential for maintaining intestinal stem cells and intestinal homeostasis in mice, and its deletion can induce the occurrence of CRC in mice ( Mathur et al, 2017 ; Hiramatsu et al, 2019 ). Erfani also proved that ARID1A downregulation might promote CRC metastasis and epithelial cell movement by decreasing EMT-related protein E-cadherin ( Erfani et al, 2021 ). In addition to influencing colon cancer progression, abnormally altered driver genes may help explain the differences among the four subtypes in response to clinical treatment.…”

ARID1A downregulation promotes cell proliferation and migration of colon cancer via VIM activation and CDH1 suppression

“… 30 , 31 , 32 Recent research has indicated that ARID1A plays a significant function in colon cancer cell proliferation and migration via CDH1 regulation. 33 Collectively, loss expression of CDH1 and increased expression of VIM appear to contribute to the formation of metastasis via ARID1A loss of expression. 34 Furthermore, the cellular enrichment analysis of highly elevated and downregulated genes showed considerable evidence of cell–cell adhesion and mesenchymal epithelial transformation.…”