The Tumor-Suppressive Role of miR-204-5p Through Targeting Ezrin in Breast Cancer: Experimental Evidence From Cell Lines and Clinical Samples

IF 2.9 3区医学 Q2 ONCOLOGY

Clinical breast cancer Pub Date : 2025-03-19 DOI:10.1016/j.clbc.2025.02.013

Tianfu Dong , Honglei Zhou , Jinhai Tang

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引用次数: 0

Abstract

Introduction

Breast cancer (BC) remains one of the most prevalent malignancies and leading causes of cancer-related deaths among women worldwide. MicroRNA-204-5p (miR-204-5p) has been implicated in various cancers, where its downregulation is associated with adverse clinicopathological features and poor prognosis. Ezrin, a member of the ERM (Ezrin-Radixin-Moesin) family, links membrane proteins to the actin cytoskeleton and has been reported to play roles in tumor progression. However, the regulatory relationship between miR-204-5p and Ezrin in breast cancer remains unclear.

Materials and Methods

We conducted bioinformatics analyses using the TCGA BRCA dataset and GEO datasets GSE97811 and GSE144534 to evaluate the expression patterns of miR-204-5p and Ezrin. In vitro assays, including cell proliferation, migration, and invasion analyses, were performed to assess the functional effects of miR-204-5p in BC cells. Western blotting and luciferase reporter assays were used to confirm the regulatory relationship between miR-204-5p, Ezrin, and the AKT signaling pathway.

Results

miR-204-5p was significantly downregulated in breast cancer tissues and was associated with aggressive tumor characteristics and poor patient prognosis. Conversely, Ezrin was upregulated in BC tissues and identified as a direct target of miR-204-5p. Overexpression of miR-204-5p inhibited BC cell proliferation, migration, and invasion, while also reducing Ezrin expression. Mechanistic studies indicated that suppression of Ezrin by miR-204-5p led to downregulation of the AKT signaling pathway.

Conclusion

Our findings demonstrate that miR-204-5p functions as a tumor suppressor in breast cancer by targeting Ezrin and inhibiting the AKT pathway. This suggests a potential therapeutic role for miR-204-5p in the treatment of breast cancer.

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miR-204-5p通过靶向Ezrin在乳腺癌中的肿瘤抑制作用：来自细胞系和临床样本的实验证据

乳腺癌（BC）仍然是最普遍的恶性肿瘤之一，也是全世界妇女癌症相关死亡的主要原因。MicroRNA-204-5p （miR-204-5p）与多种癌症有关，其下调与不良的临床病理特征和不良预后有关。Ezrin是ERM （Ezrin- radixin - moesin）家族的一员，将膜蛋白与肌动蛋白细胞骨架连接起来，并在肿瘤进展中发挥作用。然而，miR-204-5p和Ezrin在乳腺癌中的调控关系尚不清楚。材料和方法：我们使用TCGA BRCA数据集和GEO数据集GSE97811和GSE144534进行生物信息学分析，评估miR-204-5p和Ezrin的表达模式。通过体外实验，包括细胞增殖、迁移和侵袭分析，评估miR-204-5p在BC细胞中的功能作用。Western blotting和荧光素酶报告基因检测证实miR-204-5p、Ezrin和AKT信号通路之间的调控关系。结果：miR-204-5p在乳腺癌组织中显著下调，与肿瘤侵袭性特征和患者预后不良相关。相反，Ezrin在BC组织中上调，并被确定为miR-204-5p的直接靶点。过表达miR-204-5p抑制BC细胞增殖、迁移和侵袭，同时也降低Ezrin的表达。机制研究表明，miR-204-5p抑制Ezrin导致AKT信号通路下调。结论：我们的研究结果表明，miR-204-5p通过靶向Ezrin并抑制AKT通路在乳腺癌中发挥抑瘤作用。这表明miR-204-5p在乳腺癌治疗中具有潜在的治疗作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical breast cancer 医学-肿瘤学

CiteScore

5.40

自引率

3.20%

发文量

174

审稿时长

48 days

期刊介绍： Clinical Breast Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of breast cancer. Clinical Breast Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of breast cancer. The main emphasis is on recent scientific developments in all areas related to breast cancer. Specific areas of interest include clinical research reports from various therapeutic modalities, cancer genetics, drug sensitivity and resistance, novel imaging, tumor genomics, biomarkers, and chemoprevention strategies.