Abstract
Over 95% of human genes are alternatively spliced, expressing splice isoforms that often exhibit antagonistic functions. We describe genes whose alternative splicing has been linked to prostate cancer; namely VEGFA, KLF6, BCL2L2, ERG, and AR. We discuss opportunities to develop novel therapies that target specific splice isoforms, or that target the machinery of splicing. Therapeutic approaches include the development of small molecule inhibitors of splice factor kinases, splice isoform specific siRNAs, and splice switching oligonucleotides.
Keywords:
AR; BCL2L2; ERG; KLF6; RNA interference; VEGFA; alternative splicing; prostate cancer; splice factor kinases; splice factors; splice switching oligonucleotides.
MeSH terms
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Alternative Splicing*
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Genetic Therapy / methods*
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Humans
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Kruppel-Like Factor 6 / genetics
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Kruppel-Like Factor 6 / metabolism
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Male
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Prostatic Neoplasms / genetics*
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Prostatic Neoplasms / therapy
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Receptors, Androgen / genetics
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Receptors, Androgen / metabolism
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Transcriptional Regulator ERG / genetics
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Transcriptional Regulator ERG / metabolism
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Apoptosis Regulatory Proteins
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BCL2L2 protein, human
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ERG protein, human
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KLF6 protein, human
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Kruppel-Like Factor 6
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Receptors, Androgen
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Transcriptional Regulator ERG
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VEGFA protein, human
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Vascular Endothelial Growth Factor A