Dual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells

In ovarian cancer, therapy resistance mechanisms complicate cancer cell eradication. Targeting Musashi RNA-binding proteins (MSI) may increase therapeutic efficacy. Database analyses were performed to identify gene expression associations between MSI proteins and key therapy resistance and cancer st...

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Autores principales:	Maria T. Löblein, Isabel Falke, Hans Theodor Eich, Burkhard Greve, Martin Götte, Fabian M. Troschel
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ovarian cancer therapy resistance cancer stem cell Musashi radioresistance notch Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/fba844a38927480bb007b581decb3f53
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spelling	oai:doaj.org-article:fba844a38927480bb007b581decb3f532021-11-11T16:57:53ZDual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells10.3390/ijms2221115021422-00671661-6596https://doaj.org/article/fba844a38927480bb007b581decb3f532021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11502https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067In ovarian cancer, therapy resistance mechanisms complicate cancer cell eradication. Targeting Musashi RNA-binding proteins (MSI) may increase therapeutic efficacy. Database analyses were performed to identify gene expression associations between MSI proteins and key therapy resistance and cancer stem cell (CSC) genes. Then, ovarian cancer cells were subjected to siRNA-based dual knockdown of MSI-1 and MSI-2. CSC and cell cycle gene expression was investigated using quantitative polymerase chain reaction (qPCR), western blots, and flow cytometry. Metabolic activity and chemoresistance were assessed by MTT assay. Clonogenic assays were used to quantify cell survival post-irradiation. Database analyses demonstrated positive associations between MSI proteins and putative CSC markers NOTCH, MYC, and ALDH4A1 and negative associations with NOTCH inhibitor NUMB. MSI-2 expression was negatively associated with the apoptosis regulator p21. MSI-1 and MSI-2 were positively correlated, informing subsequent dual knockdown experiments. After MSI silencing, CSC genes were downregulated, while cell cycle progression was reduced. Metabolic activity was decreased in some cancer cells. Both chemo- and radioresistance were reduced after dual knockdown, suggesting therapeutic potential. Dual knockdown of MSI proteins is a promising venue to impede tumor growth and sensitize ovarian cancer cells to irradiation and chemotherapy.Maria T. LöbleinIsabel FalkeHans Theodor EichBurkhard GreveMartin GötteFabian M. TroschelMDPI AGarticleovarian cancertherapy resistancecancer stem cellMusashiradioresistancenotchBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11502, p 11502 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ovarian cancer therapy resistance cancer stem cell Musashi radioresistance notch Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ovarian cancer therapy resistance cancer stem cell Musashi radioresistance notch Biology (General) QH301-705.5 Chemistry QD1-999 Maria T. Löblein Isabel Falke Hans Theodor Eich Burkhard Greve Martin Götte Fabian M. Troschel Dual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells
description	In ovarian cancer, therapy resistance mechanisms complicate cancer cell eradication. Targeting Musashi RNA-binding proteins (MSI) may increase therapeutic efficacy. Database analyses were performed to identify gene expression associations between MSI proteins and key therapy resistance and cancer stem cell (CSC) genes. Then, ovarian cancer cells were subjected to siRNA-based dual knockdown of MSI-1 and MSI-2. CSC and cell cycle gene expression was investigated using quantitative polymerase chain reaction (qPCR), western blots, and flow cytometry. Metabolic activity and chemoresistance were assessed by MTT assay. Clonogenic assays were used to quantify cell survival post-irradiation. Database analyses demonstrated positive associations between MSI proteins and putative CSC markers NOTCH, MYC, and ALDH4A1 and negative associations with NOTCH inhibitor NUMB. MSI-2 expression was negatively associated with the apoptosis regulator p21. MSI-1 and MSI-2 were positively correlated, informing subsequent dual knockdown experiments. After MSI silencing, CSC genes were downregulated, while cell cycle progression was reduced. Metabolic activity was decreased in some cancer cells. Both chemo- and radioresistance were reduced after dual knockdown, suggesting therapeutic potential. Dual knockdown of MSI proteins is a promising venue to impede tumor growth and sensitize ovarian cancer cells to irradiation and chemotherapy.
format	article
author	Maria T. Löblein Isabel Falke Hans Theodor Eich Burkhard Greve Martin Götte Fabian M. Troschel
author_facet	Maria T. Löblein Isabel Falke Hans Theodor Eich Burkhard Greve Martin Götte Fabian M. Troschel
author_sort	Maria T. Löblein
title	Dual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells
title_short	Dual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells
title_full	Dual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells
title_fullStr	Dual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells
title_full_unstemmed	Dual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells
title_sort	dual knockdown of musashi rna-binding proteins msi-1 and msi-2 attenuates putative cancer stem cell characteristics and therapy resistance in ovarian cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fba844a38927480bb007b581decb3f53
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Dual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells

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