Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor
<p>STAT5B, a specific member of the STAT family, is intimately associated with prostate tumor progression. While the full form of STAT5B is thought to promote tumor progression, a naturally occurring truncated isoform acts as a tumor suppressor. We previously demonstrated that truncated STAT5...
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| Format: | Article |
| Language: | English |
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Ivyspring International Publisher
2013-01-01
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| Series: | International Journal of Biological Sciences |
| Online Access: | http://www.biolsci.org/v09p0045.htm |
| _version_ | 1818358270418485248 |
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| author | Aleksandra Shchelkunova, Boris Ermolinsky, Meghan Boyle, Ivan Mendez, Michael Lehker, Karen S. Martirosyan, Alexander V. Kazansky |
| author_facet | Aleksandra Shchelkunova, Boris Ermolinsky, Meghan Boyle, Ivan Mendez, Michael Lehker, Karen S. Martirosyan, Alexander V. Kazansky |
| author_sort | Aleksandra Shchelkunova, Boris Ermolinsky, Meghan Boyle, Ivan Mendez, Michael Lehker, Karen S. Martirosyan, Alexander V. Kazansky |
| collection | DOAJ |
| description | <p>STAT5B, a specific member of the STAT family, is intimately associated with prostate tumor progression. While the full form of STAT5B is thought to promote tumor progression, a naturally occurring truncated isoform acts as a tumor suppressor. We previously demonstrated that truncated STAT5 is generated by insertion of an alternatively spliced exon and results in the introduction of an early termination codon. Present approaches targeting STAT proteins based on inhibition of functional domains of STAT's, such as DNA-binding, cooperative binding (protein-protein interaction), dimerization and phosphorylation will halt the action of the entire gene, both the proto-oncogenic and tumor suppressor functions of Stat5B.</p><p>In this report we develop a new approach aimed at inhibiting the expression of full-length STAT5B (a proto-oncogene) while simultaneously enhancing the expression of STAT5∆B (a tumor suppressor). We have demonstrated the feasibility of using steric-blocking splice-switching oligonucleotides (SSOs) with a complimentary sequence to the targeted exon-intron boundary to enhance alternative intron/exon retention (up to 10%). The functional effect of the intron/exon proportional tuning was validated by cell proliferation and clonogenic assays. The new scheme applies specific steric-blocking splice-switching oligonucleotides and opens an opportunity for anti-tumor treatment as well as for the alteration of functional abilities of other STAT proteins.</p> |
| first_indexed | 2024-12-13T20:26:20Z |
| format | Article |
| id | doaj.art-7583544725754c248b4bd3a8e68f6760 |
| institution | Directory Open Access Journal |
| issn | 1449-2288 |
| language | English |
| last_indexed | 2024-12-13T20:26:20Z |
| publishDate | 2013-01-01 |
| publisher | Ivyspring International Publisher |
| record_format | Article |
| series | International Journal of Biological Sciences |
| spelling | doaj.art-7583544725754c248b4bd3a8e68f67602022-12-21T23:32:33ZengIvyspring International PublisherInternational Journal of Biological Sciences1449-22882013-01-01914554Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor SuppressorAleksandra Shchelkunova, Boris Ermolinsky, Meghan Boyle, Ivan Mendez, Michael Lehker, Karen S. Martirosyan, Alexander V. Kazansky<p>STAT5B, a specific member of the STAT family, is intimately associated with prostate tumor progression. While the full form of STAT5B is thought to promote tumor progression, a naturally occurring truncated isoform acts as a tumor suppressor. We previously demonstrated that truncated STAT5 is generated by insertion of an alternatively spliced exon and results in the introduction of an early termination codon. Present approaches targeting STAT proteins based on inhibition of functional domains of STAT's, such as DNA-binding, cooperative binding (protein-protein interaction), dimerization and phosphorylation will halt the action of the entire gene, both the proto-oncogenic and tumor suppressor functions of Stat5B.</p><p>In this report we develop a new approach aimed at inhibiting the expression of full-length STAT5B (a proto-oncogene) while simultaneously enhancing the expression of STAT5∆B (a tumor suppressor). We have demonstrated the feasibility of using steric-blocking splice-switching oligonucleotides (SSOs) with a complimentary sequence to the targeted exon-intron boundary to enhance alternative intron/exon retention (up to 10%). The functional effect of the intron/exon proportional tuning was validated by cell proliferation and clonogenic assays. The new scheme applies specific steric-blocking splice-switching oligonucleotides and opens an opportunity for anti-tumor treatment as well as for the alteration of functional abilities of other STAT proteins.</p>http://www.biolsci.org/v09p0045.htm |
| spellingShingle | Aleksandra Shchelkunova, Boris Ermolinsky, Meghan Boyle, Ivan Mendez, Michael Lehker, Karen S. Martirosyan, Alexander V. Kazansky Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor International Journal of Biological Sciences |
| title | Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor |
| title_full | Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor |
| title_fullStr | Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor |
| title_full_unstemmed | Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor |
| title_short | Tuning of Alternative Splicing - Switch From Proto-Oncogene to Tumor Suppressor |
| title_sort | tuning of alternative splicing switch from proto oncogene to tumor suppressor |
| url | http://www.biolsci.org/v09p0045.htm |
| work_keys_str_mv | AT aleksandrashchelkunovaborisermolinskymeghanboyleivanmendezmichaellehkerkarensmartirosyanalexandervkazansky tuningofalternativesplicingswitchfromprotooncogenetotumorsuppressor |