Dong Tianfu, Zhou Honglei, Tang Jinhai
Lianyungang Clinical College of Nanjing Medical University, The First People Hospital of Lianyungang City, Lianyungang, China; Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Clin Breast Cancer. 2025 Jul;25(5):e588-e596. doi: 10.1016/j.clbc.2025.02.013. Epub 2025 Mar 19.
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.
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.
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.
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.
乳腺癌（BC）仍然是全球女性中最常见的恶性肿瘤之一，也是癌症相关死亡的主要原因。微小RNA-204-5p（miR-204-5p）已被证明与多种癌症有关，其下调与不良的临床病理特征和预后不良相关。埃兹蛋白是ERM（埃兹蛋白-根蛋白-膜突蛋白）家族的成员，它将膜蛋白与肌动蛋白细胞骨架相连，据报道在肿瘤进展中发挥作用。然而，miR-204-5p与埃兹蛋白在乳腺癌中的调控关系仍不清楚。
我们使用TCGA BRCA数据集以及GEO数据集GSE97811和GSE144534进行生物信息学分析，以评估miR-204-5p和埃兹蛋白的表达模式。进行了体外实验，包括细胞增殖、迁移和侵袭分析，以评估miR-204-5p在乳腺癌细胞中的功能作用。采用蛋白质免疫印迹法和荧光素酶报告基因实验来确认miR-204-5p、埃兹蛋白和AKT信号通路之间的调控关系。
miR-204-5p在乳腺癌组织中显著下调，并且与侵袭性肿瘤特征和患者预后不良相关。相反，埃兹蛋白在乳腺癌组织中上调，并被确定为miR-204-5p的直接靶点。miR-204-5p的过表达抑制了乳腺癌细胞的增殖、迁移和侵袭，同时也降低了埃兹蛋白的表达。机制研究表明，miR-204-5p对埃兹蛋白的抑制导致AKT信号通路的下调。
我们的研究结果表明，miR-204-5p通过靶向埃兹蛋白并抑制AKT通路在乳腺癌中发挥肿瘤抑制作用。这表明miR-204-5p在乳腺癌治疗中具有潜在的治疗作用。
