Antitumour Activity of the Ribonuclease Binase from <i>Bacillus pumilus</i> in the RLS<sub>40</sub> Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning
The important role of miRNA in cell proliferation and differentiation has raised interest in exogenous ribonucleases (RNases) as tools to control tumour-associated intracellular and extracellular miRNAs. In this work, we evaluated the effects of the RNase binase from <i>Bacillus pumilus</i&...
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2020-11-01
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author | Islam Saber Ead Mohamed Aleksandra V. Sen’kova Alsu I. Nadyrova Innokenty A. Savin Andrey V. Markov Vladimir A. Mitkevich Aleksander A. Makarov Olga N. Ilinskaya Nadezhda L. Mironova Marina A. Zenkova |
author_facet | Islam Saber Ead Mohamed Aleksandra V. Sen’kova Alsu I. Nadyrova Innokenty A. Savin Andrey V. Markov Vladimir A. Mitkevich Aleksander A. Makarov Olga N. Ilinskaya Nadezhda L. Mironova Marina A. Zenkova |
author_sort | Islam Saber Ead Mohamed |
collection | DOAJ |
description | The important role of miRNA in cell proliferation and differentiation has raised interest in exogenous ribonucleases (RNases) as tools to control tumour-associated intracellular and extracellular miRNAs. In this work, we evaluated the effects of the RNase binase from <i>Bacillus pumilus</i> on small non-coding regulatory RNAs in the context of mouse RLS<sub>40</sub> lymphosarcoma inhibition. In vitro binase exhibited cytotoxicity towards RLS<sub>40</sub> cells via apoptosis induction through caspase-3/caspase-7 activation and decreased the levels of miR-21a, let-7g, miR-31 and miR-155. Intraperitoneal injections of binase in RLS<sub>40</sub>-bearing mice resulted in the retardation of primary tumour growth by up to 60% and inhibition of metastasis in the liver by up to 86%, with a decrease in reactive inflammatory infiltration and mitosis in tumour tissue. In the blood serum of binase-treated mice, decreases in the levels of most studied miRNAs were observed, excluding let-7g, while in tumour tissue, the levels of oncomirs miR-21, miR-10b, miR-31 and miR-155, and the oncosuppressor let-7g, were upregulated. Analysis of binase-susceptible miRNAs and their regulatory networks showed that the main modulated events were transcription and translation control, the cell cycle, cell proliferation, adhesion and invasion, apoptosis and autophagy, as well as some other tumour-related cascades, with an impact on the observed antitumour effects. |
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spelling | doaj.art-5447cbac80b4402c8796f22b3b9411ba2023-11-20T19:33:59ZengMDPI AGBiomolecules2218-273X2020-11-011011150910.3390/biom10111509Antitumour Activity of the Ribonuclease Binase from <i>Bacillus pumilus</i> in the RLS<sub>40</sub> Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal FunctioningIslam Saber Ead Mohamed0Aleksandra V. Sen’kova1Alsu I. Nadyrova2Innokenty A. Savin3Andrey V. Markov4Vladimir A. Mitkevich5Aleksander A. Makarov6Olga N. Ilinskaya7Nadezhda L. Mironova8Marina A. Zenkova9Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaInstitute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, RussiaThe important role of miRNA in cell proliferation and differentiation has raised interest in exogenous ribonucleases (RNases) as tools to control tumour-associated intracellular and extracellular miRNAs. In this work, we evaluated the effects of the RNase binase from <i>Bacillus pumilus</i> on small non-coding regulatory RNAs in the context of mouse RLS<sub>40</sub> lymphosarcoma inhibition. In vitro binase exhibited cytotoxicity towards RLS<sub>40</sub> cells via apoptosis induction through caspase-3/caspase-7 activation and decreased the levels of miR-21a, let-7g, miR-31 and miR-155. Intraperitoneal injections of binase in RLS<sub>40</sub>-bearing mice resulted in the retardation of primary tumour growth by up to 60% and inhibition of metastasis in the liver by up to 86%, with a decrease in reactive inflammatory infiltration and mitosis in tumour tissue. In the blood serum of binase-treated mice, decreases in the levels of most studied miRNAs were observed, excluding let-7g, while in tumour tissue, the levels of oncomirs miR-21, miR-10b, miR-31 and miR-155, and the oncosuppressor let-7g, were upregulated. Analysis of binase-susceptible miRNAs and their regulatory networks showed that the main modulated events were transcription and translation control, the cell cycle, cell proliferation, adhesion and invasion, apoptosis and autophagy, as well as some other tumour-related cascades, with an impact on the observed antitumour effects.https://www.mdpi.com/2218-273X/10/11/1509RNasesbinasecytotoxicitymiRNAsantitumour activitytumour models |
spellingShingle | Islam Saber Ead Mohamed Aleksandra V. Sen’kova Alsu I. Nadyrova Innokenty A. Savin Andrey V. Markov Vladimir A. Mitkevich Aleksander A. Makarov Olga N. Ilinskaya Nadezhda L. Mironova Marina A. Zenkova Antitumour Activity of the Ribonuclease Binase from <i>Bacillus pumilus</i> in the RLS<sub>40</sub> Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning Biomolecules RNases binase cytotoxicity miRNAs antitumour activity tumour models |
title | Antitumour Activity of the Ribonuclease Binase from <i>Bacillus pumilus</i> in the RLS<sub>40</sub> Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning |
title_full | Antitumour Activity of the Ribonuclease Binase from <i>Bacillus pumilus</i> in the RLS<sub>40</sub> Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning |
title_fullStr | Antitumour Activity of the Ribonuclease Binase from <i>Bacillus pumilus</i> in the RLS<sub>40</sub> Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning |
title_full_unstemmed | Antitumour Activity of the Ribonuclease Binase from <i>Bacillus pumilus</i> in the RLS<sub>40</sub> Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning |
title_short | Antitumour Activity of the Ribonuclease Binase from <i>Bacillus pumilus</i> in the RLS<sub>40</sub> Tumour Model Is Associated with the Reorganisation of the miRNA Network and Reversion of Cancer-Related Cascades to Normal Functioning |
title_sort | antitumour activity of the ribonuclease binase from i bacillus pumilus i in the rls sub 40 sub tumour model is associated with the reorganisation of the mirna network and reversion of cancer related cascades to normal functioning |
topic | RNases binase cytotoxicity miRNAs antitumour activity tumour models |
url | https://www.mdpi.com/2218-273X/10/11/1509 |
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