环状 RNA KIF4A 通过 miR-152/ZEB1 轴促进乳腺癌细胞迁移、侵袭并抑制细胞凋亡。
Circular RNA KIF4A promotes cell migration, invasion and inhibits apoptosis through miR-152/ZEB1 axis in breast cancer.
机构信息
Institute of Nursing and Health, College of Nursing and Health of Henan University, Kaifeng, China.
Department of Teaching Management, School of Medicine of Kaifeng City, Kaifeng, China.
出版信息
Diagn Pathol. 2020 May 14;15(1):55. doi: 10.1186/s13000-020-00963-7.
BACKGROUND
Circular RNAs (circRNAs) have been demonstrated to exert crucial mediators in tumor initiation and development. Nevertheless, the roles of circKIF4A in breast cancer (BC) are still not very clear.
METHODS
Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of circKIF4A, miR-152, zinc finger E-box binding homeobox 1 (ZEB1) mRNA and caspase-3. Western blot assay was utilized to examine the protein level of ZEB1. Transwell assay and flow-cytometric analysis were adopted for the evaluation of cell migration, invasion and apoptosis, respectively. The associations among circKIF4A, miR-152 and ZEB1 were predicted by online websites and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.
RESULTS
CircKIF4A and ZEB1 were conspicuously upregulated and miR-152 was markedly reduced in BC tissues and cells. Deficiency of circKIF4A repressed migration, invasion and induced apoptosis of BC cells. Moreover, circKIF4A was confirmed to be a sponge of miR-152 and miR-152 could bind to ZEB1. MiR-152 inhibition or ZEB1 overexpression abolished the impacts of circKIF4A knockdown on cell migration, invasion and apoptosis in BC.
CONCLUSION
Silencing of circKIF4A hampered cell metastasis and promoted apoptosis by regulating ZEB1 via sponging miR-152 in BC.
背景
环状 RNA（circRNAs）已被证明在肿瘤的发生和发展中发挥着重要的调节作用。然而，circKIF4A 在乳腺癌（BC）中的作用尚不清楚。
方法
采用实时定量聚合酶链反应（qRT-PCR）检测 circKIF4A、miR-152、锌指 E 盒结合同源盒 1（ZEB1）mRNA 和半胱天冬酶-3 的表达。采用 Western blot 检测 ZEB1 蛋白水平。采用 Transwell 检测和流式细胞术分别评估细胞迁移、侵袭和凋亡。通过在线网站预测 circKIF4A、miR-152 和 ZEB1 之间的关联，并通过双荧光素酶报告基因检测和 RNA 免疫沉淀（RIP）检测验证。
结果
circKIF4A 和 ZEB1 在 BC 组织和细胞中显著上调，miR-152 显著下调。circKIF4A 缺失抑制了 BC 细胞的迁移、侵袭，并诱导其凋亡。此外，circKIF4A 被证实是 miR-152 的海绵体，miR-152 可以与 ZEB1 结合。miR-152 抑制或 ZEB1 过表达消除了 circKIF4A 敲低对 BC 细胞迁移、侵袭和凋亡的影响。
结论
沉默 circKIF4A 通过海绵吸附 miR-152 调节 ZEB1 抑制 BC 细胞转移并促进细胞凋亡。
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