Сборник содержит материалы научной мультиконференции «Биотех- нология медицине будущего»

Antitumor activity of exogenous ribonucleases in vitro and in vivo:
the search for molecular targets among miRNAs
Mohamed I.S.
1,2
, Nadyrova A.
3
, Sen’kova A.V.
1
, Zenkova M.A.
1
, Mironova N.L.
1
1
Institute of chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia 
2
Novosibirsk State University, Novosibirsk, Russia 
3
Institute of Fundamental Medicine and Biology, Kazan Federal (Volga-Region) University, 
Kazan, Russia
Exogenous ribonucleases (RNases) have potential cytotoxicity on cancer cells due to their 
ability to destroy RNA and, consequently, inhibit protein biosynthesis at the transcriptional 
and translational levels. Also, the use of RNases as anticancer therapy helps to balance patho-
logical molecular changes occurring in tumor cells and thus control their malignant behavior. 
Here, we investigated the ability of exogenous ribonucleases to reduce the invasive potential 
of B16 melanoma and A549 in vitro. It was found that binase had a cytotoxic effect on MCF-7 
breast cancer cell line (IC
30
≈ 200 µg/ml). Also, the cytotoxic effect of binase on HeLa cells was 
revealed (IC
10 
≈ 15 µg/ml). At the same time, binase reduced the rate of cell migration by 1.5-2 
times depending on the dose used compared to the control. Significantly lower doses of RNase A
(2.5 - 5 µg/ml) inhibited the migratory activity of A549 cells.
The change in the miRNA profile of melanoma B16 cells was assessed under the action of 
binase and RNase A 
in vitro.
It was shown that expression levels of tumor suppressor miRNAs 
were upregulated and oncomir miRNAs were downregulated after treatment with Binase and 
RNase A. 
In experimental model of drug-resistant lymphosarcoma RLS40 of mice it was shown that 
binase and RNase A caused 3-fold retardation of primary tumor growth and essential decrease 
in metastases area in the liver. In the tumor tissue of mice bearing RLS
40
after treatment with 
binase, it was shown that binase as well as RNase A caused the upregulation of both oncomirs 
and tumour-suppressor microRNAs, including microRNAs of the let-7 family, known to 
negatively regulate tumour progression. While in the blood serum of mice bearing RLS
40
, 
binase caused the decrease of oncomir levels and increase in tumour-suppressor microRNAs 
(let-7g). These results coincide with results obtained for RNase A in model of Lewis ling 
carcinoma of mice.
Our results suggest that ribonucleases change balance between oncogenic and tumour-
suppressor miRNAs brings to the reduction of tumour malignancy resulting in inhibition of 
tumour growth and metastasis. In conclusion, these two exogenous ribonucleases can be used 
both as promising antitumor therapeutics and tools for search for miRNA among oncomirs 
overexpressed upon tumor progression that can be targeted by antisense oligonucleotides or 
their derivatives.
This work was supported by Russian State funded budget project of ICBFM SB RAS
# АААА-А17-117020210024-8 and grant RFBR no. 17-00-00059.

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Всероссийская мультиконференция с международным участием «Биотехнология – медицине будущего»
29 июня - 2 июля 2019 г., г. Новосибирск, Россия
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