The Role And Molecular Mechanism Of SLC26A9 In The Initiation And Development Of Triple Negative Breast Cancer

Objective: SLC26A9 is a member of the SLC26 A family of bicarbonate transporters,involved in the regulation of bicarbonate secretion and chloride ion transport.Previous studies have shown that the absence of SLC26A9 in the stomach can lead to the occurrence and development of gastric cancer.However,the expression and function of SLC26A9 in triple-negative breast cancer remain unclear.Therefore,this study aims to study the potential role of SLC26A9 in the pathogenesis of triple-negative breast cancer(TNBC),and to provide a new theoretical and scientific basis for the therapeutic target of TNBC.Methods: 1)Immunohistochemistry was used to detect the expression of SLC26A9 in TNBC tissues and adjacent tissues.Using WB to detect the expression of SLC26A9 in human breast normal epithelial cell line and human TNBC cell lines;2)To analyze the relationship between the expression of SLC26A9 and the clinicopathological characteristics and prognosis of TNBC patients;3)Construct SLC26A9 knockout or knockdown TNBC cell line,and use PCR or WB to verify the knockout or knockdown efficiency;4)Cell functional experiments were used to detect the effects of SLC26A9 knockout or knockdown on the proliferation,apoptosis,cell cycle and migration of TNBC cells;5)Detect the effects of knockout or knockdown of SLC26A9 on EGFR/PI3 K signaling pathway and downstream proteins in TNBC cells by WB;6)Add EGF as an agonist to further clarify whether SLC26A9 plays a role by activating the EGFR/PI3 K signaling pathway.Results: 1)The expression of SLC26A9 was significantly up-regulated in TNBC tissues and cells,and compared with the low expression group,OS of the high expression group was significantly reduced;2)Knockout or knockdown of SLC26A9 can block the G2/M transition,induce apoptosis,and inhibit the proliferation,migration of TNBC cells(MDA-MB-231 and MDA-MB-468);3)SLC26A9 knockout or knockdown can inhibit the expression of the proliferation marker,EMT marker snail and downstream stroma related proteins,and promote the expression of epithelial related proteins such as E-cadherin;4)Knockout or knockdown of SLC26A9 inhibits the expression of key proteins in the EGFR/PI3 K signaling pathway of TNBC cells.Conclusion: This study shows that the expression of SLC26A9 is significantly up-regulated in TNBC tissues and cells,and is associated with poor prognosis.The OS of patients in the SLC26A9 high expression group was significantly reduced.Further mechanism studies have shown that SLC26A9 can block the G2/M cycle transition,inhibiting apoptosis,and promoting its proliferation and migration of TNBC cells by activating the EGFR/PI3 K signaling pathway.It suggests that SLC26A9 may play a role in the occurrence and development of TNBC,and is expected to provide a new direction for the therapy of TNBC.