ARID1A regulates E-cadherin expression in colorectal cancer cells: a promising candidate therapeutic target
ARID1A regulates E-cadherin expression in colorectal cancer cells: a promising candidate therapeutic target
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DOI：
10.1007/s11033-021-06671-9
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发表时间：
2021-08-23
影响因子：
2.8
通讯作者：
Mokarram, Pooneh
中科院分区：
文献类型：
--
作者：
Erfani, Mehran;Zamani, Mozhdeh;Mokarram, Pooneh
背景转移是结直肠癌（CRC）患者死亡的主要原因，而上皮-间质转化（EMT）是肿瘤转移的重要环节。ARID 1A是一种真正的肿瘤抑制基因，其表达下调在促进EMT和CRC转移中起重要作用，但其分子机制尚不清楚。在这里，我们评估了ARID 1A敲低和过表达对人CRC细胞中EMT相关基因E-钙粘蛋白和β-连环蛋白表达的影响。方法与结果采用实时定量PCR（qPCR）和western blot检测ARID 1A、E-cadherin和beta-catenin在结直肠癌细胞系中的表达水平。进行ARID 1A过表达和shRNA介导的敲低以表明ARID 1A表达对CRC细胞系中E-钙粘蛋白和β-连环蛋白表达的影响。使用伤口愈合测定评估ARID 1A敲低对HCT 116细胞迁移能力的影响。我们发现，粘附蛋白E-cadherin的mRNA和蛋白表达显着下调响应于shRNA介导的ARID 1A敲低在HCT 116和HT 29细胞。相反，ARID 1A在SW 48细胞中的过表达显著增加了E-钙粘蛋白的表达。此外，ARID 1A沉默促进HCT 116细胞的迁移。ARID 1A敲低和过表达并不改变β-连环蛋白的表达水平。结论E-cadherin水平与ARID 1A表达密切相关。因此，ARID 1A下调可能通过减少EMT相关蛋白E-cadherin和促进上皮细胞运动来促进CRC转移。ARID 1A可能代表CRC的有希望的候选治疗靶点。
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.