Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer.
TMPRSS2-ERG junction oncogene is present in more than 50% of patients with prostate cancer and its expression is frequently associated with poor prognosis. Our aim is to achieve gene knockdown by siRNA TMPRSS2-ERG and then to assess the biological consequences of this inhibition. First, we designed...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4416711?pdf=render |
| _version_ | 1818265526780035072 |
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| author | Giorgia Urbinati Hafiz Muhammad Ali Quentin Rousseau Hubert Chapuis Didier Desmaële Patrick Couvreur Liliane Massaad-Massade |
| author_facet | Giorgia Urbinati Hafiz Muhammad Ali Quentin Rousseau Hubert Chapuis Didier Desmaële Patrick Couvreur Liliane Massaad-Massade |
| author_sort | Giorgia Urbinati |
| collection | DOAJ |
| description | TMPRSS2-ERG junction oncogene is present in more than 50% of patients with prostate cancer and its expression is frequently associated with poor prognosis. Our aim is to achieve gene knockdown by siRNA TMPRSS2-ERG and then to assess the biological consequences of this inhibition. First, we designed siRNAs against the two TMPRSS2-ERG fusion variants (III and IV), most frequently identified in patients' biopsies. Two of the five siRNAs tested were found to efficiently inhibit mRNA of both TMPRSS2-ERG variants and to decrease ERG protein expression. Microarray analysis further confirmed ERG inhibition by both siRNAs TMPRSS2-ERG and revealed one common down-regulated gene, ADRA2A, involved in cell proliferation and migration. The siRNA against TMPRSS2-ERG fusion variant IV showed the highest anti-proliferative effects: Significantly decreased cell viability, increased cleaved caspase-3 and inhibited a cluster of anti-apoptotic proteins. To propose a concrete therapeutic approach, siRNA TMPRSS2-ERG IV was conjugated to squalene, which can self-organize as nanoparticles in water. The nanoparticles of siRNA TMPRSS2-ERG-squalene injected intravenously in SCID mice reduced growth of VCaP xenografted tumours, inhibited oncoprotein expression and partially restored differentiation (decrease in Ki67). In conclusion, this study offers a new prospect of treatment for prostate cancer based on siRNA-squalene nanoparticles targeting TMPRSS2-ERG junction oncogene. |
| first_indexed | 2024-12-12T19:52:13Z |
| format | Article |
| id | doaj.art-33214af9472444a8ba4fd0881641bb0d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T19:52:13Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-33214af9472444a8ba4fd0881641bb0d2022-12-22T00:13:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012527710.1371/journal.pone.0125277Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer.Giorgia UrbinatiHafiz Muhammad AliQuentin RousseauHubert ChapuisDidier DesmaëlePatrick CouvreurLiliane Massaad-MassadeTMPRSS2-ERG junction oncogene is present in more than 50% of patients with prostate cancer and its expression is frequently associated with poor prognosis. Our aim is to achieve gene knockdown by siRNA TMPRSS2-ERG and then to assess the biological consequences of this inhibition. First, we designed siRNAs against the two TMPRSS2-ERG fusion variants (III and IV), most frequently identified in patients' biopsies. Two of the five siRNAs tested were found to efficiently inhibit mRNA of both TMPRSS2-ERG variants and to decrease ERG protein expression. Microarray analysis further confirmed ERG inhibition by both siRNAs TMPRSS2-ERG and revealed one common down-regulated gene, ADRA2A, involved in cell proliferation and migration. The siRNA against TMPRSS2-ERG fusion variant IV showed the highest anti-proliferative effects: Significantly decreased cell viability, increased cleaved caspase-3 and inhibited a cluster of anti-apoptotic proteins. To propose a concrete therapeutic approach, siRNA TMPRSS2-ERG IV was conjugated to squalene, which can self-organize as nanoparticles in water. The nanoparticles of siRNA TMPRSS2-ERG-squalene injected intravenously in SCID mice reduced growth of VCaP xenografted tumours, inhibited oncoprotein expression and partially restored differentiation (decrease in Ki67). In conclusion, this study offers a new prospect of treatment for prostate cancer based on siRNA-squalene nanoparticles targeting TMPRSS2-ERG junction oncogene.http://europepmc.org/articles/PMC4416711?pdf=render |
| spellingShingle | Giorgia Urbinati Hafiz Muhammad Ali Quentin Rousseau Hubert Chapuis Didier Desmaële Patrick Couvreur Liliane Massaad-Massade Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer. PLoS ONE |
| title | Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer. |
| title_full | Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer. |
| title_fullStr | Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer. |
| title_full_unstemmed | Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer. |
| title_short | Antineoplastic Effects of siRNA against TMPRSS2-ERG Junction Oncogene in Prostate Cancer. |
| title_sort | antineoplastic effects of sirna against tmprss2 erg junction oncogene in prostate cancer |
| url | http://europepmc.org/articles/PMC4416711?pdf=render |
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