Research output: Contribution to journal › Article › peer-review
Antitumour activity of the ribonuclease binase from bacillus pumilus in the RLS40 tumour model is associated with the reorganisation of the miRNA network and reversion of cancer‐related cascades to normal functioning. / Mohamed, Islam Saber Ead; Sen’kova, Aleksandra V.; Nadyrova, Alsu I. et al.
In: Biomolecules, Vol. 10, No. 11, 1509, 11.2020, p. 1-20.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Antitumour activity of the ribonuclease binase from bacillus pumilus in the RLS40 tumour model is associated with the reorganisation of the miRNA network and reversion of cancer‐related cascades to normal functioning
AU - Mohamed, Islam Saber Ead
AU - Sen’kova, Aleksandra V.
AU - Nadyrova, Alsu I.
AU - Savin, Innokenty A.
AU - Markov, Andrey V.
AU - Mitkevich, Vladimir A.
AU - Makarov, Aleksander A.
AU - Ilinskaya, Olga N.
AU - Mironova, Nadezhda L.
AU - Zenkova, Marina A.
N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/11
Y1 - 2020/11
N2 - 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 Bacillus pumilus on small non‐coding regulatory RNAs in the context of mouse RLS40 lymphosarcoma inhibition. In vitro binase exhibited cytotoxicity towards RLS40 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 RLS40‐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.
AB - 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 Bacillus pumilus on small non‐coding regulatory RNAs in the context of mouse RLS40 lymphosarcoma inhibition. In vitro binase exhibited cytotoxicity towards RLS40 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 RLS40‐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.
KW - Antitumour activity
KW - Binase
KW - Cytotoxicity
KW - MiRNAs
KW - RNases
KW - Tumour models
KW - APOPTOSIS
KW - miRNAs
KW - ONCONASE
KW - DOWN-REGULATION
KW - MICRORNAS
KW - tumour models
KW - RNASE
KW - IN-VITRO
KW - antitumour activity
KW - GROWTH
KW - binase
KW - EXPRESSION
KW - cytotoxicity
UR - http://www.scopus.com/inward/record.url?scp=85095439556&partnerID=8YFLogxK
U2 - 10.3390/biom10111509
DO - 10.3390/biom10111509
M3 - Article
C2 - 33147876
AN - SCOPUS:85095439556
VL - 10
SP - 1
EP - 20
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 11
M1 - 1509
ER -
ID: 26005939