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Role of MicroRNAs in Regulation of Cellular Response to Hypoxia

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Abstract

Hypoxia causes changes in transcription of the genes that contribute to adaptation of the cells to low levels of oxygen. The main mechanism regulating cellular response to hypoxia is activation of hypoxia-inducible transcription factors (HIF), which include several isoforms and control expression of more than a thousand genes. HIF activity is regulated at various levels, including by small non-coding RNA molecules called microRNAs (miRNAs). miRNAs regulate cellular response to hypoxia by influencing activation of HIF, its degradation, and translation of HIF-dependent proteins. At the same time, HIFs also affect miRNAs biogenesis. Data on the relationship of a particular HIF isoform with miRNAs are contradictory, since studies have been performed using different cell lines, various types of experimental animals and clinical material, as well as at different oxygen concentrations and durations of hypoxic exposure. In addition, HIF expression may be affected by the initial resistance of organisms to lack of oxygen, which has not been taken into account in the studies. This review analyzes the data on the effect of hypoxia on biogenesis and functioning of miRNAs, as well as on the effect of miRNAs on mRNAs of the genes involved in adaptation to oxygen deficiency. Understanding the mechanisms of relationship between HIF, hypoxia, and miRNA is necessary to develop new approaches to personalized therapy for diseases accompanied by oxygen deficiency.

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Abbreviations

AGO:

Argonaute family proteins

CTAD:

C-terminal transactivation domain

FIH:

factor inhibiting HIF

HIF:

hypoxia-inducible factor

HREs:

hypoxia response elements

LPS:

lipopolysaccharide

mTOR:

mammalian target of rapamycin

miRNA:

microRNA

NF-κB:

nuclear factor kappa B

NTAD:

N-terminal transactivation domain

ODDD:

oxygen-dependent degradation domain

PHDs:

prolyl hydroxylases

pVHL:

protein Von Hippel–Lindau

RISC:

RNA-induced silencing complex

VEGF:

vascular endothelial growth factor

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Funding

This work was financially supported by the State Budget Project no. 122030200530-6 “Cellular and molecular-biological mechanisms of inflammation in the development of socially significant human diseases”.

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  1. Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, 117418, Moscow, Russia

    Maria V. Silina, Dzhuliia Sh. Dzhalilova & Olga V. Makarova

  2. Faculty of Biology, Lomonosov Moscow State University, 119234, Moscow, Russia

    Olga V. Makarova

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  1. Maria V. Silina
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  2. Dzhuliia Sh. Dzhalilova
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M.V.S. – literature data analysis, preparing the manuscript and figures, D.S.D. – literature data discussion and editing of the manuscript, O.V.M. – final text editing.

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Correspondence to Maria V. Silina.

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Silina, M.V., Dzhalilova, D.S. & Makarova, O.V. Role of MicroRNAs in Regulation of Cellular Response to Hypoxia. Biochemistry Moscow 88, 741–757 (2023). https://doi.org/10.1134/S0006297923060032

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