# Time-Dependent Loss of miR-548c-3p and Activation of E2F3/FOXM1 in Breast Cancer: In Vitro and TCGA-Based Evidence for a Post-Transcriptional Mechanism

## TL;DR

This study shows how the loss of miR-548c-3p over time leads to increased activity of cancer-related genes E2F3 and FOXM1 in breast cancer cells.

## Contribution

The paper identifies a time-dependent post-transcriptional mechanism linking miR-548c-3p loss to E2F3/FOXM1 activation in breast cancer.

## Key findings

- miR-548c-3p levels decrease progressively over time in breast cancer cells.
- E2F3 and FOXM1 are upregulated as miR-548c-3p declines, suggesting post-transcriptional derepression.
- High E2F3 and FOXM1 expression correlates with poor survival in breast cancer patients.

## Abstract

MicroRNAs are key post-transcriptional regulators in breast cancer, but their time-dependent dynamics and downstream oncogenic effects are not fully understood. miR-548c-3p has been proposed as a tumor suppressor, yet its temporal behavior and impact on cell cycle drivers remain unclear. This study investigated the time-dependent expression of miR-548c-3p and its post-transcriptional regulation of E2F3 and FOXM1 in MCF-7 breast cancer cells. Cells were analyzed at multiple time points (2–72 h) by quantitative real-time PCR to assess dynamic changes in miR-548c-3p, E2F3, and FOXM1 mRNA levels. Bioinformatic validation using TCGA-BRCA datasets and public platforms evaluated gene expression, promoter methylation, and prognostic significance. miR-548c-3p showed a progressive time-dependent decline, with the lowest levels at 72 h, whereas E2F3 and FOXM1 were significantly upregulated over time, supporting a post-transcriptional derepression mechanism. TCGA-based analyses confirmed overexpression and hypomethylation of E2F3 and FOXM1 in breast cancer, particularly in triple-negative tumors, and high expression of both genes was associated with poor survival. These findings indicate that time-dependent loss of miR-548c-3p contributes to E2F3 and FOXM1 activation through a post-transcriptional regulatory mechanism, highlighting this miRNA–oncogene axis as a potential prognostic signature and therapeutic target in breast cancer.