CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma

Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the conte...
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Autor*in:	S. John Liu [verfasserIn] Martina Malatesta [verfasserIn] Brian V. Lien [verfasserIn] Parna Saha [verfasserIn] Shivani S. Thombare [verfasserIn] Sung Jun Hong [verfasserIn] Leslie Pedraza [verfasserIn] Mark Koontz [verfasserIn] Kyounghee Seo [verfasserIn] Max A. Horlbeck [verfasserIn] Daniel He [verfasserIn] Harjus S. Birk [verfasserIn] Miten Jain [verfasserIn] Hugh E. Olsen [verfasserIn] Mark Akeson [verfasserIn] Jonathan S. Weissman [verfasserIn] Michelle Monje [verfasserIn] Nalin Gupta [verfasserIn] David R. Raleigh [verfasserIn] Erik M. Ullian [verfasserIn] Daniel A. Lim [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	CRISPRi lncRNA Organoids Radiation Glioma Cancer therapy

Übergeordnetes Werk:	In: Genome Biology - BMC, 2014, 21(2020), 1, Seite 18
Übergeordnetes Werk:	volume:21 ; year:2020 ; number:1 ; pages:18

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13059-020-01995-4

Katalog-ID:	DOAJ001201182

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245	1	0	\|a CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma
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520			\|a Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. Results We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. Conclusions These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy.
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700	0		\|a Daniel A. Lim \|e verfasserin \|4 aut
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allfields	10.1186/s13059-020-01995-4 doi (DE-627)DOAJ001201182 (DE-599)DOAJ158146c58ea3458da92657b2d5201345 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 S. John Liu verfasserin aut CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. Results We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. Conclusions These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy. CRISPRi lncRNA Organoids Radiation Glioma Cancer therapy Biology (General) Genetics Martina Malatesta verfasserin aut Brian V. Lien verfasserin aut Parna Saha verfasserin aut Shivani S. Thombare verfasserin aut Sung Jun Hong verfasserin aut Leslie Pedraza verfasserin aut Mark Koontz verfasserin aut Kyounghee Seo verfasserin aut Max A. Horlbeck verfasserin aut Daniel He verfasserin aut Harjus S. Birk verfasserin aut Miten Jain verfasserin aut Hugh E. Olsen verfasserin aut Mark Akeson verfasserin aut Jonathan S. Weissman verfasserin aut Michelle Monje verfasserin aut Nalin Gupta verfasserin aut David R. Raleigh verfasserin aut Erik M. Ullian verfasserin aut Daniel A. Lim verfasserin aut In Genome Biology BMC, 2014 21(2020), 1, Seite 18 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:21 year:2020 number:1 pages:18 https://doi.org/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/article/158146c58ea3458da92657b2d5201345 kostenfrei http://link.springer.com/article/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 1 18
spelling	10.1186/s13059-020-01995-4 doi (DE-627)DOAJ001201182 (DE-599)DOAJ158146c58ea3458da92657b2d5201345 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 S. John Liu verfasserin aut CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. Results We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. Conclusions These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy. CRISPRi lncRNA Organoids Radiation Glioma Cancer therapy Biology (General) Genetics Martina Malatesta verfasserin aut Brian V. Lien verfasserin aut Parna Saha verfasserin aut Shivani S. Thombare verfasserin aut Sung Jun Hong verfasserin aut Leslie Pedraza verfasserin aut Mark Koontz verfasserin aut Kyounghee Seo verfasserin aut Max A. Horlbeck verfasserin aut Daniel He verfasserin aut Harjus S. Birk verfasserin aut Miten Jain verfasserin aut Hugh E. Olsen verfasserin aut Mark Akeson verfasserin aut Jonathan S. Weissman verfasserin aut Michelle Monje verfasserin aut Nalin Gupta verfasserin aut David R. Raleigh verfasserin aut Erik M. Ullian verfasserin aut Daniel A. Lim verfasserin aut In Genome Biology BMC, 2014 21(2020), 1, Seite 18 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:21 year:2020 number:1 pages:18 https://doi.org/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/article/158146c58ea3458da92657b2d5201345 kostenfrei http://link.springer.com/article/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 1 18
allfields_unstemmed	10.1186/s13059-020-01995-4 doi (DE-627)DOAJ001201182 (DE-599)DOAJ158146c58ea3458da92657b2d5201345 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 S. John Liu verfasserin aut CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. Results We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. Conclusions These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy. CRISPRi lncRNA Organoids Radiation Glioma Cancer therapy Biology (General) Genetics Martina Malatesta verfasserin aut Brian V. Lien verfasserin aut Parna Saha verfasserin aut Shivani S. Thombare verfasserin aut Sung Jun Hong verfasserin aut Leslie Pedraza verfasserin aut Mark Koontz verfasserin aut Kyounghee Seo verfasserin aut Max A. Horlbeck verfasserin aut Daniel He verfasserin aut Harjus S. Birk verfasserin aut Miten Jain verfasserin aut Hugh E. Olsen verfasserin aut Mark Akeson verfasserin aut Jonathan S. Weissman verfasserin aut Michelle Monje verfasserin aut Nalin Gupta verfasserin aut David R. Raleigh verfasserin aut Erik M. Ullian verfasserin aut Daniel A. Lim verfasserin aut In Genome Biology BMC, 2014 21(2020), 1, Seite 18 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:21 year:2020 number:1 pages:18 https://doi.org/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/article/158146c58ea3458da92657b2d5201345 kostenfrei http://link.springer.com/article/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 1 18
allfieldsGer	10.1186/s13059-020-01995-4 doi (DE-627)DOAJ001201182 (DE-599)DOAJ158146c58ea3458da92657b2d5201345 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 S. John Liu verfasserin aut CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. Results We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. Conclusions These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy. CRISPRi lncRNA Organoids Radiation Glioma Cancer therapy Biology (General) Genetics Martina Malatesta verfasserin aut Brian V. Lien verfasserin aut Parna Saha verfasserin aut Shivani S. Thombare verfasserin aut Sung Jun Hong verfasserin aut Leslie Pedraza verfasserin aut Mark Koontz verfasserin aut Kyounghee Seo verfasserin aut Max A. Horlbeck verfasserin aut Daniel He verfasserin aut Harjus S. Birk verfasserin aut Miten Jain verfasserin aut Hugh E. Olsen verfasserin aut Mark Akeson verfasserin aut Jonathan S. Weissman verfasserin aut Michelle Monje verfasserin aut Nalin Gupta verfasserin aut David R. Raleigh verfasserin aut Erik M. Ullian verfasserin aut Daniel A. Lim verfasserin aut In Genome Biology BMC, 2014 21(2020), 1, Seite 18 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:21 year:2020 number:1 pages:18 https://doi.org/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/article/158146c58ea3458da92657b2d5201345 kostenfrei http://link.springer.com/article/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 1 18
allfieldsSound	10.1186/s13059-020-01995-4 doi (DE-627)DOAJ001201182 (DE-599)DOAJ158146c58ea3458da92657b2d5201345 DE-627 ger DE-627 rakwb eng QH301-705.5 QH426-470 S. John Liu verfasserin aut CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. Results We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. Conclusions These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy. CRISPRi lncRNA Organoids Radiation Glioma Cancer therapy Biology (General) Genetics Martina Malatesta verfasserin aut Brian V. Lien verfasserin aut Parna Saha verfasserin aut Shivani S. Thombare verfasserin aut Sung Jun Hong verfasserin aut Leslie Pedraza verfasserin aut Mark Koontz verfasserin aut Kyounghee Seo verfasserin aut Max A. Horlbeck verfasserin aut Daniel He verfasserin aut Harjus S. Birk verfasserin aut Miten Jain verfasserin aut Hugh E. Olsen verfasserin aut Mark Akeson verfasserin aut Jonathan S. Weissman verfasserin aut Michelle Monje verfasserin aut Nalin Gupta verfasserin aut David R. Raleigh verfasserin aut Erik M. Ullian verfasserin aut Daniel A. Lim verfasserin aut In Genome Biology BMC, 2014 21(2020), 1, Seite 18 (DE-627)326173617 (DE-600)2040529-7 1474760X nnns volume:21 year:2020 number:1 pages:18 https://doi.org/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/article/158146c58ea3458da92657b2d5201345 kostenfrei http://link.springer.com/article/10.1186/s13059-020-01995-4 kostenfrei https://doaj.org/toc/1474-760X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 1 18
language	English
source	In Genome Biology 21(2020), 1, Seite 18 volume:21 year:2020 number:1 pages:18
sourceStr	In Genome Biology 21(2020), 1, Seite 18 volume:21 year:2020 number:1 pages:18
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	CRISPRi lncRNA Organoids Radiation Glioma Cancer therapy Biology (General) Genetics
isfreeaccess_bool	true
container_title	Genome Biology
authorswithroles_txt_mv	S. John Liu @@aut@@ Martina Malatesta @@aut@@ Brian V. Lien @@aut@@ Parna Saha @@aut@@ Shivani S. Thombare @@aut@@ Sung Jun Hong @@aut@@ Leslie Pedraza @@aut@@ Mark Koontz @@aut@@ Kyounghee Seo @@aut@@ Max A. Horlbeck @@aut@@ Daniel He @@aut@@ Harjus S. Birk @@aut@@ Miten Jain @@aut@@ Hugh E. Olsen @@aut@@ Mark Akeson @@aut@@ Jonathan S. Weissman @@aut@@ Michelle Monje @@aut@@ Nalin Gupta @@aut@@ David R. Raleigh @@aut@@ Erik M. Ullian @@aut@@ Daniel A. Lim @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	326173617
id	DOAJ001201182
language_de	englisch
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John Liu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. 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callnumber-first	Q - Science
author	S. John Liu
spellingShingle	S. John Liu misc QH301-705.5 misc QH426-470 misc CRISPRi misc lncRNA misc Organoids misc Radiation misc Glioma misc Cancer therapy misc Biology (General) misc Genetics CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma
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topic_title	QH301-705.5 QH426-470 CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma CRISPRi lncRNA Organoids Radiation Glioma Cancer therapy
topic	misc QH301-705.5 misc QH426-470 misc CRISPRi misc lncRNA misc Organoids misc Radiation misc Glioma misc Cancer therapy misc Biology (General) misc Genetics
topic_unstemmed	misc QH301-705.5 misc QH426-470 misc CRISPRi misc lncRNA misc Organoids misc Radiation misc Glioma misc Cancer therapy misc Biology (General) misc Genetics
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title	CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma
ctrlnum	(DE-627)DOAJ001201182 (DE-599)DOAJ158146c58ea3458da92657b2d5201345
title_full	CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma
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author_browse	S. John Liu Martina Malatesta Brian V. Lien Parna Saha Shivani S. Thombare Sung Jun Hong Leslie Pedraza Mark Koontz Kyounghee Seo Max A. Horlbeck Daniel He Harjus S. Birk Miten Jain Hugh E. Olsen Mark Akeson Jonathan S. Weissman Michelle Monje Nalin Gupta David R. Raleigh Erik M. Ullian Daniel A. Lim
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title_sort	crispri-based radiation modifier screen identifies long non-coding rna therapeutic targets in glioma
callnumber	QH301-705.5
title_auth	CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma
abstract	Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. Results We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. Conclusions These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy.
abstractGer	Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. Results We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. Conclusions These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy.
abstract_unstemmed	Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. Results We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. Conclusions These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy.
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container_issue	1
title_short	CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma
url	https://doi.org/10.1186/s13059-020-01995-4 https://doaj.org/article/158146c58ea3458da92657b2d5201345 http://link.springer.com/article/10.1186/s13059-020-01995-4 https://doaj.org/toc/1474-760X
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author2	Martina Malatesta Brian V. Lien Parna Saha Shivani S. Thombare Sung Jun Hong Leslie Pedraza Mark Koontz Kyounghee Seo Max A. Horlbeck Daniel He Harjus S. Birk Miten Jain Hugh E. Olsen Mark Akeson Jonathan S. Weissman Michelle Monje Nalin Gupta David R. Raleigh Erik M. Ullian Daniel A. Lim
author2Str	Martina Malatesta Brian V. Lien Parna Saha Shivani S. Thombare Sung Jun Hong Leslie Pedraza Mark Koontz Kyounghee Seo Max A. Horlbeck Daniel He Harjus S. Birk Miten Jain Hugh E. Olsen Mark Akeson Jonathan S. Weissman Michelle Monje Nalin Gupta David R. Raleigh Erik M. Ullian Daniel A. Lim
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up_date	2024-07-03T19:00:55.787Z
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