Background

Circular RNAs (circRNAs) play important roles in the progression of various cancers, including breast cancer (BC). However, the role of circ_0001666 in BC remains unclear.

Objective

To explore the role of circ_0001666 in the progression of BC and reveal its potential molecular mechanism.

Methods

Real-time polymerase chain reaction was conducted to determine the expression of circ_0001666, miR-620 and with-no-lysine kinase 2 (WNK2). Cell counting kit 8 assay, flow cytometry and transwell assay were used to measure cell proliferation, apoptosis, migration and invasion. Western blot was utilized to examine the level of protein. Dual-luciferase reporter assay and RNA immunoprecipitation assay were used to verify the interaction between miR-620 and circ_0001666 or WNK2. Mice xenotransplantation models were built to explore the effect of circ_0001666 on BC tumor growth in vivo.

Results

Circ_0001666 was downregulated in BC tumor tissues and cells. Overexpressed circ_0001666 inhibited the proliferation, migration, invasion, while promoted apoptosis and tumor growth of BC in vitro or in vivo. Furthermore, circ_0001666 could serve as a sponge of miR-620. MiR-620 inhibitor hindered BC cell progression, which was similar to the effect of circ_0001666 overexpression. WNK2 was a target of miR-620, and circ_0001666 could sponge miR-620 to positive regulate WNK2. The knockdown of WNK2 reversed the effect of circ_0001666 overexpression on BC progression.

Conclusion

Circ_0001666 hindered the progression of BC via miR-620/WNK2 axis.

中文翻译：

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Circ_0001666 影响 miR-620/WNK2 轴以抑制乳腺癌进展

 背景

环状RNA（circRNA）在包括乳腺癌（BC）在内的各种癌症的进展中发挥着重要作用。然而，circ_0001666 在 BC 中的作用仍不清楚。

 客观的

探讨circ_0001666在BC进展中的作用并揭示其潜在的分子机制。

 方法

进行实时聚合酶链反应以确定circ_0001666、miR-620和无赖氨酸激酶2（WNK2）的表达。采用细胞计数试剂盒8法、流式细胞术和Transwell法测定细胞增殖、凋亡、迁移和侵袭。使用蛋白质印迹来检查蛋白质水平。使用双荧光素酶报告基因测定和RNA免疫沉淀测定来验证miR-620与circ_0001666或WNK2之间的相互作用。建立小鼠异种移植模型以探讨circ_0001666对体内BC肿瘤生长的影响。

 结果

Circ_0001666 在 BC 肿瘤组织和细胞中下调。过表达的circ_0001666在体外或体内抑制BC的增殖、迁移、侵袭，同时促进细胞凋亡和肿瘤生长。此外，circ_0001666可以充当miR-620的海绵。 MiR-620抑制剂阻碍BC细胞进展，这与circ_0001666过表达的效果相似。 WNK2是miR-620的靶标，circ_0001666可以海绵miR-620来正向调节WNK2。 WNK2 的敲除逆转了 circ_0001666 过度表达对 BC 进展的影响。

 结论

Circ_0001666 通过 miR-620/WNK2 轴阻碍 BC 的进展。