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miR-191-5p 通过抑制 KLF6 促进乳腺癌上皮间质转化。

MiR-191-5p inhibits KLF6 to promote epithelial-mesenchymal transition in breast cancer.

出版信息

Technol Health Care. 2023;31(6):2251-2265. doi: 10.3233/THC-230217.

DOI:10.3233/THC-230217
PMID:37545272
Abstract

BACKGROUND

MicroRNAs (miRNAs) exert certain functions in the development of several cancers and can be a potential hallmark for cancer diagnosis and prognosis. MiR-191-5p has been proven to have high expression in breast cancer (BC), while its biological role and potential regulatory mechanisms in BC remain an open issue.

OBJECTIVE

Bioinformatics was utilized to assay miR-191-5p level in BC tissues and predict its downstream target gene as well as the enriched signaling pathways of the target gene.

METHODS

qRT-PCR was carried out to assay miR-191-5p and KLF6 levels in BC cells as well as miR-191-5p level in blood-derived exosomes from BC patients. Western blot was to examine the expression of proteins linked with cell adhesion, epithelial-mesenchymal transition (EMT), and exosome markers. A dual luciferase reporter assay was utilized to verify the interaction between miR-191-5p and KLF6. Abilities of cell phenotypes of BC cells were detected by CCK8, Transwell, and cell adhesion assay, separately.

RESULTS

Upregulated miR-191-5p expression and downregulated KLF6 expression were observed in BC cells. There was a targeting relationship between miR-191-5p and KLF6. MiR-191-5p negatively regulated KLF6 to promote EMT and malignant progression of BC cells. Additionally, we described a dramatically high level of miR-191-5p in the blood exosomes of BC patients.

CONCLUSION

MiR-191-5p advances the EMT of BC by targeting KLF6, indicating that miR-191-5p and KLF6 may be new biomarkers for BC.

摘要

背景

MicroRNAs(miRNAs)在几种癌症的发展中发挥一定作用,并且可能成为癌症诊断和预后的潜在标志。miR-191-5p 在乳腺癌(BC)中被证明高表达,但其在 BC 中的生物学功能和潜在调控机制仍未解决。

目的

利用生物信息学方法检测 BC 组织中 miR-191-5p 的水平,并预测其下游靶基因以及靶基因的富集信号通路。

方法

通过 qRT-PCR 检测 BC 细胞中 miR-191-5p 和 KLF6 的水平以及 BC 患者血液衍生外泌体中的 miR-191-5p 水平。Western blot 检测与细胞黏附、上皮间质转化(EMT)和外泌体标志物相关的蛋白表达。双荧光素酶报告基因实验验证 miR-191-5p 与 KLF6 的相互作用。分别通过 CCK8、Transwell 和细胞黏附实验检测 BC 细胞表型的能力。

结果

BC 细胞中 miR-191-5p 表达上调,KLF6 表达下调。miR-191-5p 与 KLF6 之间存在靶向关系。miR-191-5p 通过负调控 KLF6 促进 EMT 和 BC 细胞的恶性进展。此外,我们描述了 BC 患者血液外泌体中 miR-191-5p 水平的显著升高。

结论

miR-191-5p 通过靶向 KLF6 促进 BC 的 EMT,表明 miR-191-5p 和 KLF6 可能是 BC 的新生物标志物。

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