环状 RNA 0001666 通过调控 miR-620/WNK2 轴抑制乳腺癌进展。
Circ_0001666 affects miR-620/WNK2 axis to inhibit breast cancer progression.
机构信息
Department of Clinical Laboratory, The First People's Hospital of Jingmen, No. 67 Xiangshan Avenue, Jingmen, 448000, Hubei, China.
Department of Nephropathy, Jingmen No. 2 People's Hospital, Jingmen, Hubei, China.
出版信息
Genes Genomics. 2021 Aug;43(8):947-959. doi: 10.1007/s13258-021-01114-y. Epub 2021 Jun 1.
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.
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 中的作用尚不清楚。
目的
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
实时聚合酶链反应测定 circ_0001666、miR-620 和无赖氨酸激酶 2（WNK2）的表达。细胞计数试剂盒 8 检测、流式细胞术和 Transwell 检测用于测量细胞增殖、凋亡、迁移和侵袭。Western blot 用于检测蛋白水平。双荧光素酶报告基因检测和 RNA 免疫沉淀检测用于验证 miR-620 与 circ_0001666 或 WNK2 之间的相互作用。构建小鼠异种移植模型以研究 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 circ_0001666 抑制 BC 细胞在体外和体内的增殖、迁移、侵袭，同时促进凋亡和肿瘤生长。此外，circ_0001666 可以作为 miR-620 的海绵。miR-620 抑制剂抑制 BC 细胞进展，与 circ_0001666 过表达的效果相似。WNK2 是 miR-620 的靶标，circ_0001666 可以通过海绵 miR-620 来正向调节 WNK2。WNK2 的敲低逆转了 circ_0001666 过表达对 BC 进展的影响。
结论
circ_0001666 通过 miR-620/WNK2 轴抑制 BC 的进展。
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