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

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.