Circ_0062558 promotes growth, migration, and glutamine metabolism in triple-negative breast cancer by targeting the miR-876-3p/SLC1A5 axis

被引:9
|
作者
Yuan, Mengzhen [1 ]
Zhang, Jun [1 ]
He, Yuxin [1 ]
Yi, Guangming [2 ]
Rong, Liwen [1 ]
Zheng, Liangjian [1 ]
Zhan, Tingting [1 ]
Zhou, Congming [1 ]
机构
[1] Third Peoples Hosp Chengdu, Dept Oncol, 82 Qinglong St, Chengdu 610031, Sichuan, Peoples R China
[2] Third Hosp Mianyang, Sichuan Mental Hlth Ctr, Mianyang, Sichuan, Peoples R China
关键词
CircRNA; Circ_0062558; MiR-876-3p; TNBC;
D O I
10.1007/s00404-022-06481-9
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Background Circular RNAs (circRNAs) have been reported to function as vital regulators in cancers, including triple-negative breast cancer (TNBC). This study aimed to explore the role of circ_0062558 in TNBC. Methods The real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to quantify the expressions of circ_0062558, microRNA-876-3p (miR-876-3p), and solute carrier family 1 (neutral amino acid transporter), member 5 (SLC1A5) in TNBC tissues and cells. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), thymidine analog 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, and Transwell assays were employed for cell phenotype analyses. Protein expression was tested by western blot analysis. Dual-luciferase reporter was used to confirm the association among circ_0062558, miR-876-3p, and SLC1A5 in TNBC. Xenograft experiments were performed to elucidate the function of circ_0062558 in vivo. Results TNBC tissues and cells showed the higher level of circ_0062558 when compared with control samples. Downregulation of circ_0062558 inhibited proliferation, migration, invasion, and glutamine metabolism, while enhanced apoptosis of TNBC cells, and silencing of circ_0062558 also inhibited the growth of tumor in vivo. MiR-876-3p was confirmed as a target of circ_0062558, and circ_0062558 knockdown repressed TNBC cell malignant behaviors by increasing miR-876-3p. Furthermore, miR-876-3p inhibited malignant behaviors of TNBC cells by down-regulating SLC1A5, a newly identified target of miR-876-3p. Conclusion Circ_0062558 promoted TNBC progression by enhancing proliferation, survival, migration, invasion, and glutamine metabolism via miR-876-3p/SLC1A5 axis, which was helpful for understanding the carcinogenic roles of circ_0062558.
引用
收藏
页码:1643 / 1655
页数:13
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