Concurrent targeting of MAP3K3 and BRD4 by miR-3140-3p overcomes acquired resistance to BET inhibitors in neuroblastoma cells.

ABSTRACT: Neuroblastoma (NB) harboring MYCN amplification is a refractory disease with a poor prognosis. As BRD4, an epigenetic reader belonging to the bromodomain and extra terminal domain (BET) family, drives transcription of MYCN in NB cells, BET inhibitors (BETis) are considered useful for NB therapy. However, clinical trials of BETis suggested that early acquired resistance to BETis limits their therapeutic benefit. MicroRNAs are small non-coding RNAs that mediate post-transcriptional silencing of target genes. We previously identified miR-3140-3p as a potent candidate for nucleic acid therapeutics for cancer, which directly targets BRD4. We demonstrated that miR-3140-3p suppresses tumor cell growth in MYCN-amplified NB by downregulating MYCN and MYC th

SUBMITTER: Liu C 

PROVIDER: S-EPMC8253920 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature