Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement

Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-c...
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Autor*in:	Karolina Łuczkowska [verfasserIn] Dorota Rogińska [verfasserIn] Zofia Ulańczyk [verfasserIn] Edyta Paczkowska [verfasserIn] Christian Andreas Schmidt [verfasserIn] Bogusław Machaliński [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	neuropathy bortezomib mirna microarray

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 21(2020), 1, p 350
Übergeordnetes Werk:	volume:21 ; year:2020 ; number:1, p 350

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/ijms21010350

Katalog-ID:	DOAJ013158813

Internformat


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520			\|a Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA−mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA−mRNA interactions are needed to elucidate mechanisms of bortezomib action.
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author_variant	k ł kł d r dr z u zu e p ep c a s cas b m bm
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allfields	10.3390/ijms21010350 doi (DE-627)DOAJ013158813 (DE-599)DOAJ33b7e9bf9dd94d09a76215aa105b996a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Karolina Łuczkowska verfasserin aut Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA−mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA−mRNA interactions are needed to elucidate mechanisms of bortezomib action. neuropathy bortezomib mirna microarray Biology (General) Chemistry Dorota Rogińska verfasserin aut Zofia Ulańczyk verfasserin aut Edyta Paczkowska verfasserin aut Christian Andreas Schmidt verfasserin aut Bogusław Machaliński verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 1, p 350 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:1, p 350 https://doi.org/10.3390/ijms21010350 kostenfrei https://doaj.org/article/33b7e9bf9dd94d09a76215aa105b996a kostenfrei https://www.mdpi.com/1422-0067/21/1/350 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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, p 350
spelling	10.3390/ijms21010350 doi (DE-627)DOAJ013158813 (DE-599)DOAJ33b7e9bf9dd94d09a76215aa105b996a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Karolina Łuczkowska verfasserin aut Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA−mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA−mRNA interactions are needed to elucidate mechanisms of bortezomib action. neuropathy bortezomib mirna microarray Biology (General) Chemistry Dorota Rogińska verfasserin aut Zofia Ulańczyk verfasserin aut Edyta Paczkowska verfasserin aut Christian Andreas Schmidt verfasserin aut Bogusław Machaliński verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 1, p 350 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:1, p 350 https://doi.org/10.3390/ijms21010350 kostenfrei https://doaj.org/article/33b7e9bf9dd94d09a76215aa105b996a kostenfrei https://www.mdpi.com/1422-0067/21/1/350 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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, p 350
allfields_unstemmed	10.3390/ijms21010350 doi (DE-627)DOAJ013158813 (DE-599)DOAJ33b7e9bf9dd94d09a76215aa105b996a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Karolina Łuczkowska verfasserin aut Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA−mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA−mRNA interactions are needed to elucidate mechanisms of bortezomib action. neuropathy bortezomib mirna microarray Biology (General) Chemistry Dorota Rogińska verfasserin aut Zofia Ulańczyk verfasserin aut Edyta Paczkowska verfasserin aut Christian Andreas Schmidt verfasserin aut Bogusław Machaliński verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 1, p 350 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:1, p 350 https://doi.org/10.3390/ijms21010350 kostenfrei https://doaj.org/article/33b7e9bf9dd94d09a76215aa105b996a kostenfrei https://www.mdpi.com/1422-0067/21/1/350 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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, p 350
allfieldsGer	10.3390/ijms21010350 doi (DE-627)DOAJ013158813 (DE-599)DOAJ33b7e9bf9dd94d09a76215aa105b996a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Karolina Łuczkowska verfasserin aut Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA−mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA−mRNA interactions are needed to elucidate mechanisms of bortezomib action. neuropathy bortezomib mirna microarray Biology (General) Chemistry Dorota Rogińska verfasserin aut Zofia Ulańczyk verfasserin aut Edyta Paczkowska verfasserin aut Christian Andreas Schmidt verfasserin aut Bogusław Machaliński verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 1, p 350 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:1, p 350 https://doi.org/10.3390/ijms21010350 kostenfrei https://doaj.org/article/33b7e9bf9dd94d09a76215aa105b996a kostenfrei https://www.mdpi.com/1422-0067/21/1/350 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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, p 350
allfieldsSound	10.3390/ijms21010350 doi (DE-627)DOAJ013158813 (DE-599)DOAJ33b7e9bf9dd94d09a76215aa105b996a DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Karolina Łuczkowska verfasserin aut Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA−mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA−mRNA interactions are needed to elucidate mechanisms of bortezomib action. neuropathy bortezomib mirna microarray Biology (General) Chemistry Dorota Rogińska verfasserin aut Zofia Ulańczyk verfasserin aut Edyta Paczkowska verfasserin aut Christian Andreas Schmidt verfasserin aut Bogusław Machaliński verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 1, p 350 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:1, p 350 https://doi.org/10.3390/ijms21010350 kostenfrei https://doaj.org/article/33b7e9bf9dd94d09a76215aa105b996a kostenfrei https://www.mdpi.com/1422-0067/21/1/350 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 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_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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, p 350
language	English
source	In International Journal of Molecular Sciences 21(2020), 1, p 350 volume:21 year:2020 number:1, p 350
sourceStr	In International Journal of Molecular Sciences 21(2020), 1, p 350 volume:21 year:2020 number:1, p 350
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authorswithroles_txt_mv	Karolina Łuczkowska @@aut@@ Dorota Rogińska @@aut@@ Zofia Ulańczyk @@aut@@ Edyta Paczkowska @@aut@@ Christian Andreas Schmidt @@aut@@ Bogusław Machaliński @@aut@@
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callnumber-first	Q - Science
author	Karolina Łuczkowska
spellingShingle	Karolina Łuczkowska misc QH301-705.5 misc QD1-999 misc neuropathy misc bortezomib misc mirna misc microarray misc Biology (General) misc Chemistry Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement
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topic_title	QH301-705.5 QD1-999 Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement neuropathy bortezomib mirna microarray
topic	misc QH301-705.5 misc QD1-999 misc neuropathy misc bortezomib misc mirna misc microarray misc Biology (General) misc Chemistry
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title	Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement
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title_sort	molecular mechanisms of bortezomib action: novel evidence for the mirna–mrna interaction involvement
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title_auth	Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement
abstract	Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA−mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA−mRNA interactions are needed to elucidate mechanisms of bortezomib action.
abstractGer	Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA−mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA−mRNA interactions are needed to elucidate mechanisms of bortezomib action.
abstract_unstemmed	Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA−mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA−mRNA interactions are needed to elucidate mechanisms of bortezomib action.
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title_short	Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement
url	https://doi.org/10.3390/ijms21010350 https://doaj.org/article/33b7e9bf9dd94d09a76215aa105b996a https://www.mdpi.com/1422-0067/21/1/350 https://doaj.org/toc/1422-0067
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up_date	2024-07-03T16:05:27.560Z
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In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA−mRNA interactions influencing vital cellular functions. 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Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement

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