ArticleCancer science2010
Spliceostatin A blocks angiogenesis by inhibiting global gene expression including VEGF.
Article in Cancer science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Review
- PHF5A as a new OncoTarget and therapeutic prospects.Heliyon · 2023Review
- Research progress and therapeutic prospect of PHF5A acting as a new target for malignant tumors.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- The splicing factor SF3B4 drives proliferation and invasion in cervical cancer by regulating SPAG5.Cell death discovery · 2022Article
- SF3B4 promotes ovarian cancer progression by regulating alternative splicing of RAD52.Cell death & disease · 2022Article
- Splicing modulators elicit global translational repression by condensate-prone proteins translated from introns.Cell chemical biology · 2022Article
- Therapeutic Targeting of Alternative Splicing: A New Frontier in Cancer Treatment.Frontiers in oncology · 2022Review
- Splicing modulators: on the way from nature to clinic.The Journal of antibiotics · 2021Review
- SNRPD1 confers diagnostic and therapeutic values on breast cancers through cell cycle regulation.Cancer cell international · 2021Article
- Titration of SF3B1 Activity Reveals Distinct Effects on the Transcriptome and Cell Physiology.International journal of molecular sciences · 2020Article
- Alternative splicing in endothelial cells: novel therapeutic opportunities in cancer angiogenesis.Journal of experimental & clinical cancer research : CR · 2020Review
- Aberrant mRNA splicing generates oncogenic RNA isoforms and contributes to the development and progression of cholangiocarcinoma.Biomedical reports · 2019Article
- Splicing modulator FR901464 is a potential agent for colorectal cancer in combination therapy.Oncotarget · 2019Article
- Alternative splicing in prostate cancer.Nature reviews. Clinical oncology · 2018Review
- Inhibition of SF3B1 by molecules targeting the spliceosome results in massive aberrant exon skipping.RNA (New York, N.Y.) · 2018Article
- Modulating splicing with small molecular inhibitors of the spliceosome.Wiley interdisciplinary reviews. RNA · 2017Review
- Global analysis of pre-mRNA subcellular localization following splicing inhibition by spliceostatin A.RNA (New York, N.Y.) · 2017Article
- RQN-18690A (18-deoxyherboxidiene) targets SF3b, a spliceosome component, and inhibits angiogenesis.The Journal of antibiotics · 2016Article
- The SF3B1 inhibitor spliceostatin A (SSA) elicits apoptosis in chronic lymphocytic leukaemia cells through downregulation of Mcl-1.Leukemia · 2016Article
- Splicing inhibition decreases phosphorylation level of Ser2 in Pol II CTD.Nucleic acids research · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spliceostatin A (SSA) is a methylated derivative of an antitumor natural product FR901464, which specifically binds and inhibits the SF3b spliceosome sub-complex. To investigate the selective antitumor activity of SSA, we focused on the regulation of vascular endothelial growth factor (VEGF) mRNA, since VEGF is a key regulatory component in tumor angiogenesis and known for the intricate regulation of mRNA processing, such as alternative splicing. We found that in HeLa cells SSA reduced the amount of both mRNA and protein of VEGF. Spliceostatin A not only inhibited the splicing reaction of VEGF pre-mRNA but also reduced the total amount of VEGF's transcripts, while SSA affected GAPDH mRNA to a lesser extent. Given a significant reduction in VEGF gene expression, SSA was expected to possess anti-angiogenic activity in vivo. Indeed, SSA inhibited cancer cell-derived angiogenesis in vivo in a chicken chorioallantoic membrane (CAM) assay. The inhibition of angiogenesis with SSA was abolished by addition of exogenous VEGF. We also performed global gene expression analyses of HeLa cells and found that the expression levels of 38% of total genes including VEGF decreased to <50% of the basal levels following 16 h of SSA treatment. These results suggest that the global interference of gene expression including VEGF in tumor cells is at least one of the mechanisms by which SSA (or FR901464) exhibits its strong antitumor activity.
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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.