Exploring the Impact of miR-34b-5p on BRD4 Gene Expression in Triple-Negative Breast Cancer Cells.

Abstract

The miR-34 family is recognized for its crucial role as tumor suppressors, particularly through its interactions with oncogenic regulators such as Tumor Protein 53 (TP53). Bromodomain-containing Protein 4 (BRD4) functions as a transcriptional regulator that enhances the expression of oncogenes. In triple-negative breast cancer (TNBC), BRD4 is often found to be overexpressed and linked to poor clinical outcomes. This study is aimed at exploring the impact of miR-34b on the sensitivity of TNBC cells to BRD4 inhibition, which may also affect TP53 expression. miR-34b-5p mimics and scrambled oligonucleotides were transfected into TP53-mutant MDA-MB-231 and nonmutant MCF-7 cell lines. The expression levels of miR-34b, TP53, and BRD4 genes, along with the migration rates and sensitivity to the BRD4-specific inhibitor JQ1, were compared between the miR-34b overexpressing cells. The results showed that miR-34b overexpression led to increased TP53 expression in MDA-MB-231 cells, while a reduction was observed in MCF-7 cells. Consequently, BRD4 expression was significantly elevated in MDA-MB-231 cells, resulting in resistance to JQ1. The increase in BRD4 expression also correlated with higher migration rates compared to MCF-7 cells. In conclusion, miR-34b may have an oncogenic role by promoting the expression of BRD4 in TNBC cells. This finding aligns with prior reports indicating a negative correlation between miR-34b levels and survival rates in patients with TNBC. These insights may provide new perspectives on the role of miR-34b in the development and progression of TNBC.