ArticleCell death & disease2023
The BRD4-SRPK2-SRSF2 signal modulates the splicing efficiency of ACSL3 pre-mRNA and influences erastin-induced ferroptosis in osteosarcoma cells.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Splicing-mediated control of hnRNPD isoform switching by SRSF2 drives PD-L1-dependent immune evasion in gallbladder cancer.Oncogene · 2026Article
- Alternative Splicing of TPM1 Mediated by SRPK3 Drives Cardiac Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.Circulation · 2026Article
- Degradation of ACSL3 by influenza A virus shifts unfolded protein response from antiviral defense to viral evasion.Virologica Sinica · 2026Article
- Non-Enzymatic MGO-Glycation of SRSF2 Drives RNA Mis-Splicing.Journal of the American Chemical Society · 2026Article
- SETD8 promotes ovarian clear cell carcinoma by epigenetically activating RNA metabolism genes via H4K20me1.Scientific reports · 2026Article
- Repression of FOSL1 augments ferroptosis to overcome oxaliplatin resistance in colorectal cancer by acting on SRSF2.Molecular biology reports · 2026Article
- The multifaceted roles of the ACSL family in cancer: Metabolic reprogramming, ferroptosis regulation and tumour immune microenvironment remodelling.Clinical and translational medicine · 2026Review
- Metabolic reprogramming-related drug resistance in osteosarcoma: from molecular mechanisms to therapeutic translation.Frontiers in molecular biosciences · 2026Review
- Transcriptomic analysis reveals lung cancer and subtype-specific alternative splicing biomarkers regulated by RNA-binding proteins.Molecular therapy. Nucleic acids · 2025Article
- BRD4 silencing attenuates hemin-induced neuronal ferroptosis and inflammation via the H3K27ac-ATF3 axis in an in vitro model of cerebral hemorrhage.European journal of medical research · 2025Article
- Comprehensive multi-omics analysis of histone acetylation modulators identifies ASH1L as a novel aggressive marker for osteosarcoma.Discover oncology · 2025Article
- Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets.Journal of bone oncology · 2025Review
- Article
- Epigenetic regulation of targeted ferroptosis: A new strategy for drug development.Journal of pharmaceutical analysis · 2024Review
- Transcription factor MEF2D regulates aberrant expression of ACSL3 and enhances sorafenib resistance by inhibiting ferroptosis in HCC.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Lipid metabolism is the key to ferroptosis susceptibility. However, little is known about the underlying mechanisms in osteosarcoma cells. Functional restriction of bromodomain-containing protein 4 (BRD4) reduced the susceptibility to erastin-induced ferroptosis of osteosarcoma cells both in vitro and in vivo. Mechanically, BRD4 controls the splicing efficiency of the RNA precursor (pre-mACSL3) of ACSL3 (ACSL3) by recruiting serinerich/threonine protein kinase 2 (SRPK2) to assemble the splicing catalytic platform. Moreover, the AMP-binding domain of ACSL3 significantly influences arachidonic acid synthesis and thus determines the susceptibility to erastin-induced ferroptosis. Overall, we found a BRD4-mediated pre-mACSL3 splicing influences erastin-induced ferroptosis by affecting arachidonic acid synthesis in osteosarcoma cells. Data in this study fills some of the gap in understanding the post-transcriptional regulatory mechanisms of ACSL3 and provides new insights into the mechanisms of lipid metabolism regulation and its effect on susceptibility to ferroptosis in osteosarcoma cells.
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