Role of ARID1A in epithelial‑mesenchymal transition inbreast cancer and its effect on cell sensitivity to 5‑FU.

Abstract

The loss of function mutation of AT-rich interactive domain 1A (ARID1A) often occurs in patients with breast cancer. It has been found that ARID1A knockout can enhance both the migratory activity of renal carcinoma cells and their sensitivity to therapeutic drugs by promoting epithelial-mesenchymal transition (EMT); however, its mechanisms of action in breast cancer remain unclear. In the present study, immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) revealed that the expression of ARID1A in breast cancer tissues was significantly lower than that in paracancerous tissues, and patients with a low ARID1A expression had a lower survival rate. ARID1A was expressed at low levels in breast cancer cells. In addition, siRNA targeting ARID1A (siARID1A) and ARID1A overexpression vector were transfected into MCF7 and MDA-MB-231 cells, respectively. Proliferation assay revealed that ARID1A silencing increased cell viability and partially reversed the inhibitory effects of 5-fluorouracil (5-FU) on the MCF7 cells, while ARID1A overexpression exerted an opposite effect on the MDA-MB-231 cells. ARID1A silencing promoted proliferation, migration, invasion and angiogenesis, and partly reversed the inhibitory effects of 5-FU on cell biological behaviors, while the overexpression of ARID1A further enhanced the inhibitory effect of 5-FU on the cells. Furthermore, ARID1A regulated the migration and invasion of breast cancer cells through EMT. On the whole, the findings of the present study demonstrate that ARID1A exerts an antitumor effect on breast cancer, and its overexpression can enhance the sensitivity of breast cancer cells to 5-FU.