circ0000799经miR-1287-5p/GPX4轴调控铁死亡促进三阴乳腺癌脑转移

目的探索circ0000799经miR-1287-5p/GPX4轴对铁死亡促进三阴乳腺癌脑转移的影响机制。 方法检测circ0000799在乳腺癌细胞系及乳腺癌组织中的表达。沉默亲代三阴乳腺癌细胞MDA-MB-231和子代脑转移细胞MDA-MB-231-BM中circ0000799的表达。比较各组细胞生长、侵袭能力、脑转移结节数目。使用双荧光素酶报告基因实验验证circ0000799、miR-1287-5p、GPX4调控关系。检测circ0000799对铁死亡相关蛋白谷胱甘肽过氧化酶4(GPX4)表达和总谷胱甘肽/氧化型谷胱甘肽比的影响。 结果与人正常乳腺上皮细胞(MCF-10A)或癌旁组织比较,circ0000799在三阴乳腺癌细胞系及乳腺癌组织中上调,且在子代三阴乳腺癌细胞系及脑转移灶中上调最为显著(P＜0.05)。与sh-circCTR组比较,sh-circ0000799组细胞生长、侵袭能力降低(P＜0.05)。sh-circCTR组、sh-circ0000799组、sh-circ0000799+RSL3组脑转移结节数量依次降低(P＜0.05)。 双荧光素酶报告基因实验显示,circ0000799可与miR-1287-5p相互作用,miR-1287-5p可与GPX4相互作用。与sh-circCTR组比较,sh-circ0000799组miR-1287-5表达增加,总谷胱甘肽/氧化型谷胱甘肽比和GPX4表达降低(P＜0.05)。与miR-CTR组比较,miR-1287-5p组GPX4 mRNA表达降低(P＜0.05)。 结论circ0000799在三阴乳腺癌中高表达且可能通过miR-1287-5p/GPX4轴促进三阴乳腺癌脑转移。

circ0000799 promotes brain metastasis of triple negative breast cancer by regulating ferroptosis via miR-1287-5p/GPX4 axis

AimTo 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. MethodsThe expression of circ0000799 in breast cancer cell lines and tissues was detected. The expression of circ0000799 in parental triple negative breast cancer cell MDA-MB-231 and offspring brain metastasis cell MDA-MB-231-BM was silenced. The growth, invasion ability, and number of brain metastases in each group were compared. 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. ResultsCompared 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 negative 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). Conclusioncirc0000799 is highly expressed in triple negative breast cancer and may promote brain metastasis of triple negative breast cancer through miR-1287-5p/GPX4 axis.