The Significant Suppression of Mir-4521 and up Regulation of Foxm1 Isoforms in Breast Cancer Publisher



Kargar S ; Shahbazi S ; Geranpayeh L
Source: Journal of Kerman University of Medical Sciences Published:2026

Abstract

Introduction: As a transcription factor, FOXM1 is elaborate in diverse aspects of cancer, such as proliferation, invasion as well as metastasis. Alternative splicing creates several FOXM1 isoforms, among which FOXM1b and FOXM1c are the key transcripts evaluated. Recently, FOXM1 was reported to be direct target of miR-4521, a microRNA with a possible tumor suppressor role. In this study alterations in miR-4521 expression and its association with FOXM1b and FOXM1c were investigated in ductal carcinoma of breast. Methods: Gene expression was examined in 44 matched tumor and adjacent normal tissue samples, along with the MCF-7 cell line. By designing specific primers, the expression of two FOXM1 transcript variants and the miR-4521 gene, along with internal controls were calculated by quantitative Real-time PCR. The amplified fragments were checked via Sanger sequencing. Results: The expression of FOXM1b and FOXM1c significantly increased in tumor tissues, emphasizing the oncogenic role of both transcript variants in breast cancer. The fold change in FOXM1b and FOXM1c were 4.62 and 3.12, respectively. miR-4521 was significantly down-regulated in tumors (fold change: 0.218), which validate the tumor suppressor effect. A decrease in miR-4521 expression had a statistically significant association with the increased expression of FOXM1b and FOXM1c (P = 0.000). Conclusion: Targeting the FOXM1 transcription factor represents a promising approach to halt breast cancer progression. Our findings indicate that FOXM1b and FOXM1c might have a role in the progress of breast cancer, and miR-4521 could be a potential candidate for their suppression. © 2026 The Author(s).