circ0000799 promotes brain metastasis of triple negative breast cancer by regulating ferropto-sis via miR-1287-5p/GPX4 axis
Aim To explore the effect of circ0000799 on the promotion of brain metastasis of triple negative breast cancer by regulating ferroptosis via miR-1287-5p/GPX4 axis.Methods The expression of circ0000799 in breast cancer cell lines and tis-sues was detected.The expression of circ0000799 in parental triple negative breast cancer cell MDA-MB-231 and offspring brain me-tastasis cell MDA-MB-231-BM was silenced.The growth,invasion ability,and number of brain metastases in each group were com-pared.The regulatory relationship among circ0000799,miR-1287-5p,and GPX4 was verified by using dual luciferase reporter gene experiments.The effect of circ0000799 on the expression of iron death related protein glutathione peroxidase 4(GPX4)and the ratio of total glutathione to oxidized glutathione was assessed.Results Compared with MCF-10A and adjacent tissues,circ0000799 was gradually up-regulated in three negative breast cancer cell lines and tissues,and was most significantly up-regulated in three nega-tive breast cancer cell lines and brain metastases of the offspring(P＜0.05).Compared with the sh-circCTR group,the sh-circ0000799 group showed a decrease in cell growth and invasion ability(P＜0.05).The number of brain metastatic nodules in the sh-circCTR group,sh-circ0000799 group,and sh-circ0000799+RSL3 group decreased sequentially(P＜0.05).The dual luciferase reporter gene experiment showed that circ0000799 can interact with miR-1287-5p,miR-1287-5p can interact with GPX4 interaction.Compared with the sh-circCTR group,the sh-circ0000799 group showed an increase in miR-1287-5 expression,as well as a decrease in total glutathione/oxidized glutathione ratio and GPX4 protein expression(P＜0.05).Compared with the miR-CTR group,the miR-1287-5p group showed a decrease in GPX4 mRNA expression(P＜0.05).Conclusion circ0000799 is highly expressed in triple negative breast cancer and may promote brain metastasis of triple negative breast cancer through miR-1287-5p/GPX4 axis.
万方数据
维普
