The Role And Molecular Mechanism Of Bicarbonate Transporter SLC26A9 In The Initiation And Progression Of Breast Cancer

Objectives: Breast cancer is the highest incidence of female malignant tumor,threatening the life and health of women,and the incidence is increasing year by year.Therefore,it is particularly important to clarify its etiology and pathogenesis,find new diagnosis and effective drug targets.This study mainly studied the expression of bicarbonate transporter SLC26A9 in breast cancer tissues and cells,analyzed its relationship with clinicopathology and prognosis,and preliminarily elucidated the molecular mechanism of the up-regulation of SLC26A9 gene leading to the occurrence and development of breast cancer,providing a new theoretical and scientific basis for the etiology,diagnosis and treatment targets of breast cancer.Methods: 1)The expression of SLC26A9 in breast cancer and adjacent breast cancer tissues was detected by immunohistochemistry.WB technology was used to detect the expression of SLC26A9 in human breast cancer cell lines and human breast normal epithelial cells;2)To analyze the correlation between SLC26A9 expression and clinicopathological characteristics and prognosis of breast cancer patients;3)Construct SLC26A9 overexpressing stable transgenic strains of SKBR3 cells,and verify the over-expression efficiency by RT-qPCR and WB;4)Cell functional experiments to detect the effects of SLC26A9 overexpression on the proliferation,apoptosis,migration and invasion of SKBR3 cells;5)RT-qPCR and WB detection of SLC26A9 overexpression affect the EMT process of SKBR3 cells;6)WB was used to detect the alteration of TGF-?1/p-Smad2/p-Smad3 signaling pathway by SKBR3 cells overexpressing SLC26A9.Results: 1)SLC26A9 expression was significantly up-regulated in breast cancer tissues,and the group with high expression of SLC26A9 had poor prognosis and significantly decreased OS;2)SLC26A9 can inhibit the apoptosis of SKBR3(HER2 overexpression type)cells,and promote the proliferation,migration and invasion of SKBR3 cells;3)SLC26A9 promotes the formation of filamentous processes of SKBR3 to obtain mesenchymal-like morphology,and inhibits the expression of epithelial phenotypic markers E-cadherin and ZO-1,and promotes the expression of mesenchymal phenotypic markers Fibronectin,Snail1,N-cadherin and Vimentin;4)SLC26A9 significantly promoted the expression of TGF?1,pSmad2 and p-Smad3 in breast cancer SKBR3 cells.Conclusions: This study showed that the expression of SLC26A9 was significantly upregulated in breast cancer tissues and affected the prognosis of patients.The OS of patients in the group with high expression of SLC26A9 was significantly reduced.Further mechanistic studies have shown that SLC26A9 can promote SKBR3 cells to undergo EMT by activating the TGF?1/p-Smad2/p-Smad3 signaling pathway,thereby inhibiting SKBR3 cell apoptosis,promoting SKBR3 cell proliferation,migration and invasion.It is suggested that SLC26A9 may play a certain role in the initiation and progression of HER2 overexpression breast cancer,and may provide new targets and directions for the diagnosis and treatment of this type of breast cancer.