ArticleNature communications2020
Enhanced JunD/RSK3 signalling due to loss of BRD4/FOXD3/miR-548d-3p axis determines BET inhibition resistance.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Systematic analyses uncover plasma proteins linked to incident cardiovascular diseases.Protein & cell · 2026Article
- JUNB and JUND in Urological Cancers: A Literature Review.Current issues in molecular biology · 2025Review
- Exosomes From Intestinal Epithelial Cells Promote Hepatic Differentiation of Liver Progenitor Cells in Gut-Liver-on-a-Chip Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Advancing brain tumor therapy: unveiling the potential of PROTACs for targeted protein degradation.Cytotechnology · 2025Review
- Genomic clustering tendency of transcription factors reflects phase-separated transcriptional condensates at super-enhancers.Nucleic acids research · 2025Article
- miR-512-3p/RPS6KA2 Axis Regulates Cisplatin Resistance in Ovarian Cancer via Autophagy and Ferroptosis.Oncology research · 2025Article
- RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.Expert opinion on therapeutic targets · 2024Review
- Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).Oncology reports · 2024Article
- Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect hepatocellular carcinoma cells from oxidative stress.BMC gastroenterology · 2024Article
- ZSWIM4 inhibition improves chemosensitivity in epithelial ovarian cancer cells by suppressing intracellular glycine biosynthesis.Journal of translational medicine · 2024Article
- The potential of swine pseudorabies virus attenuated vaccine for oncolytic therapy against malignant tumors.Journal of experimental & clinical cancer research : CR · 2023Article
- mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer.JCI insight · 2023Article
- Enhanced anti-glioma efficacy of doxorubicin with BRD4 PROTAC degrader using targeted nanoparticles.Materials today. Bio · 2022Article
- Review
- ERK1/2-RSK2 Signaling in Regulation of ERα-Mediated Responses.Endocrinology · 2022Review
- MYSM1 induces apoptosis and sensitizes TNBC cells to cisplatin via RSK3-phospho-BAD pathway.Cell death discovery · 2022Article
- LncRNA-RMST Functions as a Transcriptional Co-regulator of SOX2 to Regulate miR-1251 in the Progression of Hirschsprung's Disease.Frontiers in pediatrics · 2022Article
- Epigenetic heterogeneity promotes acquired resistance to BET bromodomain inhibition in ovarian cancer.American journal of cancer research · 2021Article
- Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway.Frontiers in endocrinology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BET bromodomain inhibitors (BETi), such as JQ1, have been demonstrated to effectively kill multiple types of cancer cells. However, the underlying mechanisms for BETi resistance remain largely unknown. Our evidences show that JQ1 treatment evicts BRD4 from the FOXD3-localized MIR548D1 gene promoter, leading to repression of miR-548d-3p. The loss of miRNA restores JunD expression and subsequent JunD-dependent transcription of RPS6KA2 gene. ERK1/2/5 kinases phosphorylate RSK3 (RPS6KA2), resulting in the enrichment of activated RSK3 and blockade of JQ1 killing effect. Dual inhibition of MEKs/ERKs or single EGFR inhibition are able to mimic the effect of JunD/RSK3-knockdown to reverse BETi resistance. Collectively, our study indicates that loss of BRD4/FOXD3/miR-548d-3p axis enhances JunD/RSK3 signalling and determines BET inhibition resistance, which can be reversed by targeting EGFR-MEK1/2/5-ERK1/2/5 signalling.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.