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miR-379-5p 通过靶向 KIF4A 抑制乳腺癌的增殖、迁移和侵袭。

MiR-379-5p inhibits the proliferation, migration, and invasion of breast cancer by targeting KIF4A.

机构信息

College of Nursing, Weifang Medical University, Weifang, China.

Medicine Research Center, Weifang Medical University, Weifang, China.

出版信息

Thorac Cancer. 2022 Jul;13(13):1916-1924. doi: 10.1111/1759-7714.14437. Epub 2022 May 24.

DOI:10.1111/1759-7714.14437
PMID:35608059
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9250835/
Abstract

BACKGROUND

Many studies have shown that microRNAs (miRNAs) play an essential role in gene regulation and tumor development. This study aimed to explore the expression of miR-379-5p and its mechanisms of affecting proliferation, migration, and invasion in breast cancer (BC).

METHODS

MiRNAs and mRNAs expression data of BC and normal breast tissue samples were downloaded from the TCGA and GEO databases. qRT-PCR was used to detect the expression of miR-379-5p in human normal breast epithelial cell lines and human BC cell lines. The proliferation ability of transfected cells was detected by colony formation and EdU assays. The mobility and invasion ability of transfected cells was measured by wound healing and transwell assays. The relative protein expression of transfected cells was detected by western blot. Dual luciferase reporter assay was performed to identify the targeted binding of miR-379-5p and KIF4A.

RESULTS

MiR-379-5p was lowly expressed in BC tissue samples and BC cell lines. The target genes of miR-379-5p were involved in many cancer-related signaling pathways. PPI analysis and the cytoHubba algorithm of Cytoscape identified 10 genes as the hub genes. Survival analysis showed that only KIF4A expression in 10 hub genes was significantly associated with the prognosis of BC patients and was significantly upregulated in BC. Overexpression of miR-379-5p inhibited proliferation, migration, and invasion in the BC cell line MDA-MB-231, which could be reversed by KIF4A.

CONCLUSIONS

MiR-379-5p inhibits proliferation, migration, and invasion of BC by targeting KIF4A.

摘要

背景

许多研究表明 microRNAs(miRNAs)在基因调控和肿瘤发生中起着至关重要的作用。本研究旨在探讨 miR-379-5p 的表达及其影响乳腺癌(BC)增殖、迁移和侵袭的机制。

方法

从 TCGA 和 GEO 数据库下载 BC 和正常乳腺组织样本的 miRNA 和 mRNA 表达数据。qRT-PCR 用于检测 miR-379-5p 在人正常乳腺上皮细胞系和人 BC 细胞系中的表达。转染细胞的增殖能力通过集落形成和 EdU 测定检测。转染细胞的迁移和侵袭能力通过划痕愈合和 Transwell 测定测量。转染细胞的相对蛋白表达通过 Western blot 检测。双荧光素酶报告基因实验鉴定 miR-379-5p 和 KIF4A 的靶向结合。

结果

miR-379-5p 在 BC 组织样本和 BC 细胞系中低表达。miR-379-5p 的靶基因涉及许多癌症相关的信号通路。PPI 分析和 Cytoscape 的 cytoHubba 算法鉴定出 10 个基因作为枢纽基因。生存分析表明,仅 10 个枢纽基因中的 KIF4A 表达与 BC 患者的预后显著相关,且在 BC 中显著上调。miR-379-5p 的过表达抑制 BC 细胞系 MDA-MB-231 的增殖、迁移和侵袭,这可被 KIF4A 逆转。

结论

miR-379-5p 通过靶向 KIF4A 抑制 BC 的增殖、迁移和侵袭。

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