ArticleJournal of biomolecular screening2013
A high-throughput assay to identify small-molecule modulators of alternative pre-mRNA splicing.
Article in Journal of biomolecular screening, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Development of a comparative high-throughput screening platform for identifying glioblastoma subtype specific inhibitors.Cell insight · 2025Article
- Rational Design of an Activatable Reporter for Quantitative Imaging of RNA Aberrant SplicingMolecular therapy. Methods & clinical development · 2020Article
- A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes.Nucleic acids research · 2019Article
- PTBP3 splicing factor promotes hepatocellular carcinoma by destroying the splicing balance of NEAT1 and pre-miR-612.Oncogene · 2018Article
- When one becomes many-Alternative splicing in β-cell function and failure.Diabetes, obesity & metabolism · 2018Review
- PTBP1 enhances miR-101-guided AGO2 targeting to MCL1 and promotes miR-101-induced apoptosis.Cell death & disease · 2018Article
- TGF-β1 Induces Polypyrimidine Tract-Binding Protein to Alter Fibroblasts Proliferation and Fibronectin Deposition in Keloid.Scientific reports · 2016Article
- Bis-biguanide dihydrochloride inhibits intracellular replication of M. tuberculosis and controls infection in mice.Scientific reports · 2016Article
- Article
- Pharmacodynamic assays to facilitate preclinical and clinical development of pre-mRNA splicing modulatory drug candidates.Pharmacology research & perspectives · 2015Article
- Development of a Drosophila melanogaster spliceosensor system for in vivo high-throughput screening in myotonic dystrophy type 1.Disease models & mechanisms · 2014Article
- Involvement of polypyrimidine tract-binding protein (PTBP1) in maintaining breast cancer cell growth and malignant properties.Oncogenesis · 2014Article
- Concordance of deregulated mechanisms unveiled in underpowered experiments: PTBP1 knockdown case study.BMC medical genomics · 2014Article
- New insights into functional roles of the polypyrimidine tract-binding protein.International journal of molecular sciences · 2013Review
- Targeting RNA splicing for disease therapy.Wiley interdisciplinary reviews. RNAReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alternative splicing (AS) is an efficient mechanism that involves the generation of transcriptome and protein diversity from a single gene. Defects in pre-messenger RNA (mRNA) splicing are an important cause of numerous diseases, including cancer. AS of pre-mRNA as a target for cancer therapy has not been well studied. We have reported previously that a splicing factor, polypyrimidine tract-binding protein (PTB), is overexpressed in ovarian tumors compared with matched normal controls, and knockdown of PTB expression by short-hairpin RNA impairs ovarian tumor cell growth, colony formation, and invasiveness. Given the complexity of PTB's molecular functions, a chemical method for controlling PTB activity might provide a therapeutic and experimental tool. However, no commercially available PTB inhibitors have yet been described. To expand our ability to find novel inhibitors, we developed a robust, fluorometric, cell-based high-throughput screening assay in 96-well plates that reports on the splicing activity of PTB. In an attempt to use the cells for large-scale chemical screens to identify PTB modulators, we established cell lines stably expressing the reporter gene. Our results suggest that this high-throughput assay could be used to identify small-molecule modulators of PTB activity. Based on these findings and the role that upregulated PTB has on cell proliferation and malignant properties of tumors, targeting PTB for inhibition with small molecules offers a promising strategy for cancer therapy.
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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.