Journal Article

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

Azarnia, Mahnaz, Ibrahim, Mohannad Abdulameer, Jalali, Hanieh

2025

Overview

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.

• Subject: Azepines - pharmacology / Bromodomain Containing Proteins / Cell Cycle Proteins - genetics / Cell Line, Tumor / Cell Movement - drug effects / Cell Movement - genetics / Cell Proliferation - genetics / Female / Gene Expression Regulation, Neoplastic - drug effects / Humans / MCF-7 Cells / MicroRNAs - genetics / MicroRNAs - metabolism / Nuclear Proteins - genetics / Transcription Factors - biosynthesis / Transcription Factors - genetics / Transcription Factors - metabolism / Triazoles - pharmacology / Triple Negative Breast Neoplasms - genetics / Triple Negative Breast Neoplasms - metabolism / Triple Negative Breast Neoplasms - pathology / Tumor Suppressor Protein p53 - genetics / Tumor Suppressor Protein p53 - metabolism