biostudies-literatureUnknown15(3)Zhang HThe interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells <i>via</i> increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 <i>via</i> enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of exActa pharmaceutica Sinica. B1552-1570https://www.ebi.ac.uk/biostudies/studies/S-EPMC12069253biostudies-literatureBRD4 regulates m&lt;sup&gt;6&lt;/sup&gt;A of ESPL1 mRNA &lt;i&gt;via&lt;/i&gt; interaction with ALKBH5 to modulate breast cancer progression.PMC12069253Peng YLi JLu YZhang HJiang TWang HAsadikaram GYang XLu LJiang ZXie GChen ZYi CZhou DZhong KZhou JfalseBRD4 regulates m&lt;sup&gt;6&lt;/sup&gt;A of ESPL1 mRNA &lt;i&gt;via&lt;/i&gt; interaction with ALKBH5 to modulate breast cancer progression.The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells <i>via</i> increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 <i>via</i> enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of ex2025-01-01T00:00:00Z2025 Mar2026-06-01T05:22:53.875Z2026-04-08T09:35:18.394ZS-EPMC120692534037054010.1016/j.apsb.2024.12.037