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

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.