FOXM1 Drives Subtype-Specific Dysregulation of Prognostic miRNAs in Breast Cancer Cells.

Abstract

Objective Breast cancer is a heterogeneous disease comprising distinct molecular subtypes, including estrogen receptor-positive (ER+) breast cancer and triple-negative breast cancer (TNBC). MicroRNAs (miRNAs) regulate post-transcriptional gene expression and play important roles in cancer progression by functioning as oncogenic or tumor-suppressive molecules. Forkhead box M1 (FOXM1) is an oncogenic transcription factor that is frequently upregulated in aggressive breast cancers, particularly TNBC, and is associated with proliferation, invasion, metastasis, therapy resistance, and poor prognosis. Materials and Methods Clinically relevant miRNAs associated with survival in patients with ER+ and ER- breast cancer were identified using publicly available datasets. The expression levels of miR-34a-5p, miR-873-5p, miR-193b-5p, miR-330-5p, miR-10b-5p, miR-155-5p, and miR-484 were evaluated in MDA-MB-231 TNBC cells and MCF-7 ER+ breast cancer cells following FOXM1 knockdown. Results FOXM1 knockdown was associated with increased expression of several tumor-suppressive miRNAs, including miR-34a-5p, miR-873-5p, miR-193b-5p, miR-330-5p, miR-10b-5p, and miR-484, in MDA-MB-231 cells. In contrast, most of these miRNAs were not markedly altered in MCF-7 cells, except for miR-10b-5p, whose expression decreased following FOXM1 knockdown. miR-155-5p expression remained largely unchanged in both cell lines. Conclusion Our findings demonstrate that FOXM1 knockdown was associated with differential expression of clinically relevant miRNAs in the two breast cancer cell models examined. These findings suggest that FOXM1-associated alterations in miRNA expression may contribute to the aggressive phenotype of TNBC and warrant further mechanistic investigation.