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The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy

Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor...

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Autores principales: Mironova, Nadezhda, Patutina, Olga, Brenner, Evgenyi, Kurilshikov, Alexander, Vlassov, Valentin, Zenkova, Marina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667999/
https://www.ncbi.nlm.nih.gov/pubmed/29108266
http://dx.doi.org/10.18632/oncotarget.20228
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author Mironova, Nadezhda
Patutina, Olga
Brenner, Evgenyi
Kurilshikov, Alexander
Vlassov, Valentin
Zenkova, Marina
author_facet Mironova, Nadezhda
Patutina, Olga
Brenner, Evgenyi
Kurilshikov, Alexander
Vlassov, Valentin
Zenkova, Marina
author_sort Mironova, Nadezhda
collection PubMed
description Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor-bearing mice with RNase A. We identified 966 differentially expressed transcripts in LLC tumors, of which 322 were upregulated and 644 were downregulated after RNase A treatment. Many of these genes are involved in signaling pathways that regulate energy metabolism, cell-growth promoting and transforming activity, modulation of the cancer microenvironment and extracellular matrix components, and cellular proliferation and differentiation. Following RNase A treatment, we detected an upregulation of carbohydrate metabolism, inositol phosphate cascade and oxidative phosphorylation, re-arrangement of cell adhesion, cell cycle control, apoptosis, and transcription. Whereas cancer-related signaling pathways (e.g., TGF-beta, JAK/STAT, and Wnt) were downregulated following RNase A treatment, as in the case of the PI3K/AKT pathway, which is involved in the progression of non-small lung cancer. RNase A therapy resulted in the downregulation of genes that inhibit the biogenesis of some miRNAs, particularly the let-7 miRNA family. Taken together, our data suggest that the antitumor activity and decreased invasion potential of tumor cells caused by RNase A are associated with enhanced energy cascade functioning, rearrangement of cancer-related events regulating cell growth and dissemination, and attenuation of signaling pathways having tumor-promoting activity. Thus, RNase A can be proposed as a potential component of anticancer therapy with multiple modes of action.
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spelling pubmed-56679992017-11-04 The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy Mironova, Nadezhda Patutina, Olga Brenner, Evgenyi Kurilshikov, Alexander Vlassov, Valentin Zenkova, Marina Oncotarget Research Paper Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor-bearing mice with RNase A. We identified 966 differentially expressed transcripts in LLC tumors, of which 322 were upregulated and 644 were downregulated after RNase A treatment. Many of these genes are involved in signaling pathways that regulate energy metabolism, cell-growth promoting and transforming activity, modulation of the cancer microenvironment and extracellular matrix components, and cellular proliferation and differentiation. Following RNase A treatment, we detected an upregulation of carbohydrate metabolism, inositol phosphate cascade and oxidative phosphorylation, re-arrangement of cell adhesion, cell cycle control, apoptosis, and transcription. Whereas cancer-related signaling pathways (e.g., TGF-beta, JAK/STAT, and Wnt) were downregulated following RNase A treatment, as in the case of the PI3K/AKT pathway, which is involved in the progression of non-small lung cancer. RNase A therapy resulted in the downregulation of genes that inhibit the biogenesis of some miRNAs, particularly the let-7 miRNA family. Taken together, our data suggest that the antitumor activity and decreased invasion potential of tumor cells caused by RNase A are associated with enhanced energy cascade functioning, rearrangement of cancer-related events regulating cell growth and dissemination, and attenuation of signaling pathways having tumor-promoting activity. Thus, RNase A can be proposed as a potential component of anticancer therapy with multiple modes of action. Impact Journals LLC 2017-08-12 /pmc/articles/PMC5667999/ /pubmed/29108266 http://dx.doi.org/10.18632/oncotarget.20228 Text en Copyright: © 2017 Mironova et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Mironova, Nadezhda
Patutina, Olga
Brenner, Evgenyi
Kurilshikov, Alexander
Vlassov, Valentin
Zenkova, Marina
The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy
title The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy
title_full The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy
title_fullStr The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy
title_full_unstemmed The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy
title_short The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy
title_sort systemic tumor response to rnase a treatment affects the expression of genes involved in maintaining cell malignancy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667999/
https://www.ncbi.nlm.nih.gov/pubmed/29108266
http://dx.doi.org/10.18632/oncotarget.20228
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