MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells
Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of e...
Ausführliche Beschreibung
Autor*in: |
Xie, Chen [verfasserIn] |
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Format: |
Artikel |
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Sprache: |
Englisch |
Erschienen: |
2015 |
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Rechteinformationen: |
Nutzungsrecht: FEBS Letters 589 (2015) 1873-3468 © 2015 Federation of European Biochemical Societies Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. |
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Schlagwörter: |
Gene Expression Regulation, Neoplastic - physiology |
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Übergeordnetes Werk: |
Enthalten in: FEBS letters - Amsterdam [u.a.] : Elsevier, 1968, 589(2015), 15, Seite 1958-1965 |
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Übergeordnetes Werk: |
volume:589 ; year:2015 ; number:15 ; pages:1958-1965 |
Links: |
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DOI / URN: |
10.1016/j.febslet.2015.05.030 |
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OLC1965547923 |
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520 | |a Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let‐7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let‐7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let‐7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome‐dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let‐7 binding to MDM4 is implicated in the DNA damage response. Let‐7 represses MDM4 expression by directly binding to its coding sequence. DNA damage induces let‐7 expression with subsequent decrease in MDM4. A mutation found in glioma patients may disrupt the relationship between let‐7 and MDM4. Binding of let‐7 to MDM4 is implicated in the DNA damage response. | ||
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650 | 4 | |a DNA damage | |
650 | 4 | |a MicroRNA let-7 | |
650 | 4 | |a MDM4 | |
650 | 4 | |a Glioma | |
650 | 4 | |a Coding DNA sequence | |
650 | 4 | |a Gene Expression Regulation, Neoplastic - physiology | |
650 | 4 | |a Nuclear Proteins - genetics | |
650 | 4 | |a Glioma - metabolism | |
650 | 4 | |a Brain Neoplasms - pathology | |
650 | 4 | |a MicroRNAs - physiology | |
650 | 4 | |a Glioma - pathology | |
650 | 4 | |a Brain Neoplasms - genetics | |
650 | 4 | |a Glioma - genetics | |
650 | 4 | |a Proto-Oncogene Proteins - genetics | |
650 | 4 | |a Brain Neoplasms - metabolism | |
700 | 1 | |a Chen, Wei |4 oth | |
700 | 1 | |a Zhang, Mengdie |4 oth | |
700 | 1 | |a Cai, Qiuxian |4 oth | |
700 | 1 | |a Xu, Weiyi |4 oth | |
700 | 1 | |a Li, Xiaodi |4 oth | |
700 | 1 | |a Jiang, Songshan |4 oth | |
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10.1016/j.febslet.2015.05.030 doi PQ20160617 (DE-627)OLC1965547923 (DE-599)GBVOLC1965547923 (PRQ)c223X-16a9ed00577c4d281fc2b59ffae9a150b57e8b3c6319293a93898fe1e57a1a480 (KEY)0045922420150000589001501958mdm4regulationbythelet7mirnafamilyinthednadamagere DE-627 ger DE-627 rakwb eng 570 530 610 DNB Xie, Chen verfasserin aut MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let‐7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let‐7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let‐7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome‐dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let‐7 binding to MDM4 is implicated in the DNA damage response. Let‐7 represses MDM4 expression by directly binding to its coding sequence. DNA damage induces let‐7 expression with subsequent decrease in MDM4. A mutation found in glioma patients may disrupt the relationship between let‐7 and MDM4. Binding of let‐7 to MDM4 is implicated in the DNA damage response. Nutzungsrecht: FEBS Letters 589 (2015) 1873-3468 © 2015 Federation of European Biochemical Societies Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. DNA damage MicroRNA let-7 MDM4 Glioma Coding DNA sequence Gene Expression Regulation, Neoplastic - physiology Nuclear Proteins - genetics Glioma - metabolism Brain Neoplasms - pathology MicroRNAs - physiology Glioma - pathology Brain Neoplasms - genetics Glioma - genetics Proto-Oncogene Proteins - genetics Brain Neoplasms - metabolism Chen, Wei oth Zhang, Mengdie oth Cai, Qiuxian oth Xu, Weiyi oth Li, Xiaodi oth Jiang, Songshan oth Enthalten in FEBS letters Amsterdam [u.a.] : Elsevier, 1968 589(2015), 15, Seite 1958-1965 (DE-627)129522023 (DE-600)212746-5 (DE-576)014938014 0014-5793 nnns volume:589 year:2015 number:15 pages:1958-1965 http://dx.doi.org/10.1016/j.febslet.2015.05.030 Volltext http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2015.05.030/abstract http://www.ncbi.nlm.nih.gov/pubmed/26028311 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 GBV_ILN_21 GBV_ILN_70 GBV_ILN_211 GBV_ILN_2219 GBV_ILN_4012 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4305 AR 589 2015 15 1958-1965 |
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10.1016/j.febslet.2015.05.030 doi PQ20160617 (DE-627)OLC1965547923 (DE-599)GBVOLC1965547923 (PRQ)c223X-16a9ed00577c4d281fc2b59ffae9a150b57e8b3c6319293a93898fe1e57a1a480 (KEY)0045922420150000589001501958mdm4regulationbythelet7mirnafamilyinthednadamagere DE-627 ger DE-627 rakwb eng 570 530 610 DNB Xie, Chen verfasserin aut MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let‐7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let‐7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let‐7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome‐dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let‐7 binding to MDM4 is implicated in the DNA damage response. Let‐7 represses MDM4 expression by directly binding to its coding sequence. DNA damage induces let‐7 expression with subsequent decrease in MDM4. A mutation found in glioma patients may disrupt the relationship between let‐7 and MDM4. Binding of let‐7 to MDM4 is implicated in the DNA damage response. Nutzungsrecht: FEBS Letters 589 (2015) 1873-3468 © 2015 Federation of European Biochemical Societies Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. DNA damage MicroRNA let-7 MDM4 Glioma Coding DNA sequence Gene Expression Regulation, Neoplastic - physiology Nuclear Proteins - genetics Glioma - metabolism Brain Neoplasms - pathology MicroRNAs - physiology Glioma - pathology Brain Neoplasms - genetics Glioma - genetics Proto-Oncogene Proteins - genetics Brain Neoplasms - metabolism Chen, Wei oth Zhang, Mengdie oth Cai, Qiuxian oth Xu, Weiyi oth Li, Xiaodi oth Jiang, Songshan oth Enthalten in FEBS letters Amsterdam [u.a.] : Elsevier, 1968 589(2015), 15, Seite 1958-1965 (DE-627)129522023 (DE-600)212746-5 (DE-576)014938014 0014-5793 nnns volume:589 year:2015 number:15 pages:1958-1965 http://dx.doi.org/10.1016/j.febslet.2015.05.030 Volltext http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2015.05.030/abstract http://www.ncbi.nlm.nih.gov/pubmed/26028311 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 GBV_ILN_21 GBV_ILN_70 GBV_ILN_211 GBV_ILN_2219 GBV_ILN_4012 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4305 AR 589 2015 15 1958-1965 |
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10.1016/j.febslet.2015.05.030 doi PQ20160617 (DE-627)OLC1965547923 (DE-599)GBVOLC1965547923 (PRQ)c223X-16a9ed00577c4d281fc2b59ffae9a150b57e8b3c6319293a93898fe1e57a1a480 (KEY)0045922420150000589001501958mdm4regulationbythelet7mirnafamilyinthednadamagere DE-627 ger DE-627 rakwb eng 570 530 610 DNB Xie, Chen verfasserin aut MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let‐7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let‐7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let‐7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome‐dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let‐7 binding to MDM4 is implicated in the DNA damage response. Let‐7 represses MDM4 expression by directly binding to its coding sequence. DNA damage induces let‐7 expression with subsequent decrease in MDM4. A mutation found in glioma patients may disrupt the relationship between let‐7 and MDM4. Binding of let‐7 to MDM4 is implicated in the DNA damage response. Nutzungsrecht: FEBS Letters 589 (2015) 1873-3468 © 2015 Federation of European Biochemical Societies Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. DNA damage MicroRNA let-7 MDM4 Glioma Coding DNA sequence Gene Expression Regulation, Neoplastic - physiology Nuclear Proteins - genetics Glioma - metabolism Brain Neoplasms - pathology MicroRNAs - physiology Glioma - pathology Brain Neoplasms - genetics Glioma - genetics Proto-Oncogene Proteins - genetics Brain Neoplasms - metabolism Chen, Wei oth Zhang, Mengdie oth Cai, Qiuxian oth Xu, Weiyi oth Li, Xiaodi oth Jiang, Songshan oth Enthalten in FEBS letters Amsterdam [u.a.] : Elsevier, 1968 589(2015), 15, Seite 1958-1965 (DE-627)129522023 (DE-600)212746-5 (DE-576)014938014 0014-5793 nnns volume:589 year:2015 number:15 pages:1958-1965 http://dx.doi.org/10.1016/j.febslet.2015.05.030 Volltext http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2015.05.030/abstract http://www.ncbi.nlm.nih.gov/pubmed/26028311 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 GBV_ILN_21 GBV_ILN_70 GBV_ILN_211 GBV_ILN_2219 GBV_ILN_4012 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4305 AR 589 2015 15 1958-1965 |
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10.1016/j.febslet.2015.05.030 doi PQ20160617 (DE-627)OLC1965547923 (DE-599)GBVOLC1965547923 (PRQ)c223X-16a9ed00577c4d281fc2b59ffae9a150b57e8b3c6319293a93898fe1e57a1a480 (KEY)0045922420150000589001501958mdm4regulationbythelet7mirnafamilyinthednadamagere DE-627 ger DE-627 rakwb eng 570 530 610 DNB Xie, Chen verfasserin aut MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let‐7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let‐7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let‐7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome‐dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let‐7 binding to MDM4 is implicated in the DNA damage response. Let‐7 represses MDM4 expression by directly binding to its coding sequence. DNA damage induces let‐7 expression with subsequent decrease in MDM4. A mutation found in glioma patients may disrupt the relationship between let‐7 and MDM4. Binding of let‐7 to MDM4 is implicated in the DNA damage response. Nutzungsrecht: FEBS Letters 589 (2015) 1873-3468 © 2015 Federation of European Biochemical Societies Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. DNA damage MicroRNA let-7 MDM4 Glioma Coding DNA sequence Gene Expression Regulation, Neoplastic - physiology Nuclear Proteins - genetics Glioma - metabolism Brain Neoplasms - pathology MicroRNAs - physiology Glioma - pathology Brain Neoplasms - genetics Glioma - genetics Proto-Oncogene Proteins - genetics Brain Neoplasms - metabolism Chen, Wei oth Zhang, Mengdie oth Cai, Qiuxian oth Xu, Weiyi oth Li, Xiaodi oth Jiang, Songshan oth Enthalten in FEBS letters Amsterdam [u.a.] : Elsevier, 1968 589(2015), 15, Seite 1958-1965 (DE-627)129522023 (DE-600)212746-5 (DE-576)014938014 0014-5793 nnns volume:589 year:2015 number:15 pages:1958-1965 http://dx.doi.org/10.1016/j.febslet.2015.05.030 Volltext http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2015.05.030/abstract http://www.ncbi.nlm.nih.gov/pubmed/26028311 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 GBV_ILN_21 GBV_ILN_70 GBV_ILN_211 GBV_ILN_2219 GBV_ILN_4012 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4305 AR 589 2015 15 1958-1965 |
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10.1016/j.febslet.2015.05.030 doi PQ20160617 (DE-627)OLC1965547923 (DE-599)GBVOLC1965547923 (PRQ)c223X-16a9ed00577c4d281fc2b59ffae9a150b57e8b3c6319293a93898fe1e57a1a480 (KEY)0045922420150000589001501958mdm4regulationbythelet7mirnafamilyinthednadamagere DE-627 ger DE-627 rakwb eng 570 530 610 DNB Xie, Chen verfasserin aut MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let‐7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let‐7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let‐7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome‐dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let‐7 binding to MDM4 is implicated in the DNA damage response. Let‐7 represses MDM4 expression by directly binding to its coding sequence. DNA damage induces let‐7 expression with subsequent decrease in MDM4. A mutation found in glioma patients may disrupt the relationship between let‐7 and MDM4. Binding of let‐7 to MDM4 is implicated in the DNA damage response. Nutzungsrecht: FEBS Letters 589 (2015) 1873-3468 © 2015 Federation of European Biochemical Societies Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. DNA damage MicroRNA let-7 MDM4 Glioma Coding DNA sequence Gene Expression Regulation, Neoplastic - physiology Nuclear Proteins - genetics Glioma - metabolism Brain Neoplasms - pathology MicroRNAs - physiology Glioma - pathology Brain Neoplasms - genetics Glioma - genetics Proto-Oncogene Proteins - genetics Brain Neoplasms - metabolism Chen, Wei oth Zhang, Mengdie oth Cai, Qiuxian oth Xu, Weiyi oth Li, Xiaodi oth Jiang, Songshan oth Enthalten in FEBS letters Amsterdam [u.a.] : Elsevier, 1968 589(2015), 15, Seite 1958-1965 (DE-627)129522023 (DE-600)212746-5 (DE-576)014938014 0014-5793 nnns volume:589 year:2015 number:15 pages:1958-1965 http://dx.doi.org/10.1016/j.febslet.2015.05.030 Volltext http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2015.05.030/abstract http://www.ncbi.nlm.nih.gov/pubmed/26028311 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 GBV_ILN_21 GBV_ILN_70 GBV_ILN_211 GBV_ILN_2219 GBV_ILN_4012 GBV_ILN_4125 GBV_ILN_4219 GBV_ILN_4305 AR 589 2015 15 1958-1965 |
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Xie, Chen ddc 570 misc DNA damage misc MicroRNA let-7 misc MDM4 misc Glioma misc Coding DNA sequence misc Gene Expression Regulation, Neoplastic - physiology misc Nuclear Proteins - genetics misc Glioma - metabolism misc Brain Neoplasms - pathology misc MicroRNAs - physiology misc Glioma - pathology misc Brain Neoplasms - genetics misc Glioma - genetics misc Proto-Oncogene Proteins - genetics misc Brain Neoplasms - metabolism MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells |
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570 530 610 DNB MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells DNA damage MicroRNA let-7 MDM4 Glioma Coding DNA sequence Gene Expression Regulation, Neoplastic - physiology Nuclear Proteins - genetics Glioma - metabolism Brain Neoplasms - pathology MicroRNAs - physiology Glioma - pathology Brain Neoplasms - genetics Glioma - genetics Proto-Oncogene Proteins - genetics Brain Neoplasms - metabolism |
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ddc 570 misc DNA damage misc MicroRNA let-7 misc MDM4 misc Glioma misc Coding DNA sequence misc Gene Expression Regulation, Neoplastic - physiology misc Nuclear Proteins - genetics misc Glioma - metabolism misc Brain Neoplasms - pathology misc MicroRNAs - physiology misc Glioma - pathology misc Brain Neoplasms - genetics misc Glioma - genetics misc Proto-Oncogene Proteins - genetics misc Brain Neoplasms - metabolism |
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MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells |
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MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells |
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mdm4 regulation by the let‐7 mirna family in the dna damage response of glioma cells |
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MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells |
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Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let‐7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let‐7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let‐7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome‐dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let‐7 binding to MDM4 is implicated in the DNA damage response. Let‐7 represses MDM4 expression by directly binding to its coding sequence. DNA damage induces let‐7 expression with subsequent decrease in MDM4. A mutation found in glioma patients may disrupt the relationship between let‐7 and MDM4. Binding of let‐7 to MDM4 is implicated in the DNA damage response. |
abstractGer |
Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let‐7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let‐7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let‐7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome‐dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let‐7 binding to MDM4 is implicated in the DNA damage response. Let‐7 represses MDM4 expression by directly binding to its coding sequence. DNA damage induces let‐7 expression with subsequent decrease in MDM4. A mutation found in glioma patients may disrupt the relationship between let‐7 and MDM4. Binding of let‐7 to MDM4 is implicated in the DNA damage response. |
abstract_unstemmed |
Despite extensive investigation into the role of let‐7 miRNAs in pathological tumor processes, their involvement in the DNA damage response remains unclear. Here we show that most let‐7 family members down‐regulate MDM4 expression via binding to MDM4 mRNA at a conserved DNA sequence. Expression of exogenous let‐7 miRNA mimics decreased MDM4 protein but not mRNA levels. Several DNA damage reagents increased let‐7 expression, thereby decreasing MDM4 protein levels in glioma cells. Inhibition of endogenous let‐7 with antisense RNAs rescued MDM4 protein levels with or without MG132, a proteasome‐dependent degradation inhibitor. An MDM4 mutation identified in a glioma patient was associated with loss of the putative MDM4 target site. Therefore, let‐7 binding to MDM4 is implicated in the DNA damage response. Let‐7 represses MDM4 expression by directly binding to its coding sequence. DNA damage induces let‐7 expression with subsequent decrease in MDM4. A mutation found in glioma patients may disrupt the relationship between let‐7 and MDM4. Binding of let‐7 to MDM4 is implicated in the DNA damage response. |
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MDM4 regulation by the let‐7 miRNA family in the DNA damage response of glioma cells |
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http://dx.doi.org/10.1016/j.febslet.2015.05.030 http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2015.05.030/abstract http://www.ncbi.nlm.nih.gov/pubmed/26028311 |
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