The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties
The oncogene ERG encodes an ETS family transcription factor and is implicated in blood, vascular, and bone development and in prostate, blood, and bone cancer. The ERG gene is alternatively spliced; of particular interest is its cassette exon 7b which adds 24 amino acids, in frame, to the transcript...
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doaj-c8469ee482ba4a7fb856e365059e64e52020-11-24T23:44:28ZengElsevierTranslational Oncology1936-52332019-01-01121134142The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic PropertiesSamantha L. Jumbe0Sean R. Porazinski1Sebastian Oltean2Jason P. Mansell3Bahareh Vahabi4Ian D. Wilson5Michael R. Ladomery6Faculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, United KingdomFaculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, United KingdomInstitute of Biomedical & Clinical Sciences, University of Exeter Medical School, St Luke's Campus, Heavitree Rd, Exeter, EX1 2LU, United KingdomFaculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, United KingdomFaculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, United KingdomFaculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, United KingdomFaculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, United Kingdom; Address all correspondence to: Michael R. Ladomery, Faculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, United Kingdom.The oncogene ERG encodes an ETS family transcription factor and is implicated in blood, vascular, and bone development and in prostate, blood, and bone cancer. The ERG gene is alternatively spliced; of particular interest is its cassette exon 7b which adds 24 amino acids, in frame, to the transcriptional activation domain. Higher exon 7b inclusion rates are associated with increased cell proliferation and advanced prostate cancer. The 24 amino acids encoded by exon 7b show evolutionary conservation from humans to echinoderms, highlighting their functional importance. Throughout evolution, these 24 amino acids are encoded by a distinct short exon. Splice-switching oligonucleotides based on morpholino chemistry were designed to induce skipping of ERG exon 7b in MG63 osteosarcoma and VCaP prostate cancer cells. Induction of exon 7b skipping reduced cell proliferation and invasion, increased apoptosis in vitro, and reduced xenograft growth in vivo. We also show that ERG's exon 7b is required for the induction of tissue nonspecific alkaline phosphatase. Together, these findings show that the evolutionarily conserved cassette exon 7b is central to ERG's oncogenic properties.http://www.sciencedirect.com/science/article/pii/S1936523318303553 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Samantha L. Jumbe Sean R. Porazinski Sebastian Oltean Jason P. Mansell Bahareh Vahabi Ian D. Wilson Michael R. Ladomery |
spellingShingle |
Samantha L. Jumbe Sean R. Porazinski Sebastian Oltean Jason P. Mansell Bahareh Vahabi Ian D. Wilson Michael R. Ladomery The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties Translational Oncology |
author_facet |
Samantha L. Jumbe Sean R. Porazinski Sebastian Oltean Jason P. Mansell Bahareh Vahabi Ian D. Wilson Michael R. Ladomery |
author_sort |
Samantha L. Jumbe |
title |
The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties |
title_short |
The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties |
title_full |
The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties |
title_fullStr |
The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties |
title_full_unstemmed |
The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties |
title_sort |
evolutionarily conserved cassette exon 7b drives erg's oncogenic properties |
publisher |
Elsevier |
series |
Translational Oncology |
issn |
1936-5233 |
publishDate |
2019-01-01 |
description |
The oncogene ERG encodes an ETS family transcription factor and is implicated in blood, vascular, and bone development and in prostate, blood, and bone cancer. The ERG gene is alternatively spliced; of particular interest is its cassette exon 7b which adds 24 amino acids, in frame, to the transcriptional activation domain. Higher exon 7b inclusion rates are associated with increased cell proliferation and advanced prostate cancer. The 24 amino acids encoded by exon 7b show evolutionary conservation from humans to echinoderms, highlighting their functional importance. Throughout evolution, these 24 amino acids are encoded by a distinct short exon. Splice-switching oligonucleotides based on morpholino chemistry were designed to induce skipping of ERG exon 7b in MG63 osteosarcoma and VCaP prostate cancer cells. Induction of exon 7b skipping reduced cell proliferation and invasion, increased apoptosis in vitro, and reduced xenograft growth in vivo. We also show that ERG's exon 7b is required for the induction of tissue nonspecific alkaline phosphatase. Together, these findings show that the evolutionarily conserved cassette exon 7b is central to ERG's oncogenic properties. |
url |
http://www.sciencedirect.com/science/article/pii/S1936523318303553 |
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