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MIR-518a-5p靶向ZEB2以抑制乳腺癌细胞的迁移和侵袭。

MIR-518a-5p Targets ZEB2 to Suppress the Migration and Invasion of Breast-cancer Cells.

作者信息

Wang Li, Guo Ziru, Zhang Shuo, Zhang Xiaochong, Sang Meixiang, Liu Yunjiang, Shan Baoen

出版信息

Altern Ther Health Med. 2023 Jan;29(1):137-143.

PMID:35986741
Abstract

CONTEXT

Although great progress has occurred in breast cancer (BC) treatment, including chemotherapy, chemoradiotherapy, and surgical resection, the rate of patients' survival is still unsatisfactory. Multiple genes and factors have proven to contribute to BC's occurrence. Thus, it's urgent to explore the molecular mechanisms in the development and progression of BC and find possible targets for therapy.

OBJECTIVE

The study intended to assess the mechanisms of miR-518a-5p's effect on BC by targeting the zinc finger E-box-binding homeobox 2 (ZEB2) gene.

DESIGN

The research team designed a laboratory study and retrospective analysis.

SETTING

The study took place in the Department of Breast Surgery at the Xingtai People's Hospital in Xingtai, Hebei, China.

OUTCOME MEASURES

The study measured the miR-518a-5p expression in BC tissues and normal tissues using a real-time quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) test. The research team purchased the BC cells MDA-MB-231 and MCF-7 and measured the effects of the miR-518a-5p on BC cell activity as well as epithelial-mesenchymal transition (EMT) ability, using cell scratch tests and Transwell assays. The team assessed the ZEB2 protein expression and verified the targeting relationship using a Dual-Luciferase Reporter assay.

RESULTS

The miR-518a-5p expressed was low in the BC tissues and cell lines compared with adjacent normal tissues (P < .05). Overexpressing the miR-518a-5p inhibited BC-cell migration and invasion (P < .05). Moreover, the ZEB2 was the target gene for the miR-518a-5p. The Luciferase assay verified that the miR-518a-5p directly targeted the ZEB2 in BC cells (P < .05). The Transwell invasion assay, western blot analysis, and wound healing assay also showed that the miR-518a-5p inhibited BC cells by targeting ZEB2 (P < .05).

CONCLUSIONS

The miR-518a-5p suppressed BC migration, invasion, and process of EMT by regulating ZEB2. In the future, this method may be a new option for BC diagnosis and treatment. An in-depth understanding of the role of the miR-518a-5p in BC can help clinicians to understand the pathogenic mechanism of breast cancer more accurately.

摘要

背景

尽管乳腺癌(BC)治疗已取得巨大进展,包括化疗、放化疗和手术切除,但患者的生存率仍不尽人意。多种基因和因素已被证明与BC的发生有关。因此,迫切需要探索BC发生发展的分子机制,并寻找可能的治疗靶点。

目的

本研究旨在评估miR-518a-5p通过靶向锌指E盒结合同源框2(ZEB2)基因对BC的作用机制。

设计

研究团队设计了一项实验室研究和回顾性分析。

地点

该研究在中国河北省邢台市邢台市人民医院乳腺外科进行。

观察指标

本研究采用实时定量逆转录(qRT)-聚合酶链反应(PCR)检测BC组织和正常组织中miR-518a-5p的表达。研究团队购买了BC细胞MDA-MB-231和MCF-7,采用细胞划痕试验和Transwell试验检测miR-518a-5p对BC细胞活性以及上皮-间质转化(EMT)能力的影响。研究团队评估了ZEB2蛋白的表达,并采用双荧光素酶报告基因试验验证靶向关系。

结果

与相邻正常组织相比,BC组织和细胞系中miR-518a-5p的表达较低(P < 0.05)。过表达miR-518a-5p可抑制BC细胞的迁移和侵袭(P < 0.05)。此外,ZEB2是miR-518a-5p的靶基因。荧光素酶试验证实miR-518a-5p直接靶向BC细胞中的ZEB2(P < 0.05)。Transwell侵袭试验、蛋白质印迹分析和伤口愈合试验也表明,miR-518a-5p通过靶向ZEB2抑制BC细胞(P < 0.05)。

结论

miR-518a-5p通过调节ZEB2抑制BC的迁移、侵袭和EMT过程。未来,该方法可能成为BC诊断和治疗的新选择。深入了解miR-518a-5p在BC中的作用有助于临床医生更准确地了解乳腺癌的发病机制。

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