The role of microRNA in the regulation of cellular responses to hypoxia

Abstract

The impact of hypoxia causes changes in the transcription of genes that contribute to the adaptation of cells to a lack of oxygen. The main mechanism regulating the cellular response to hypoxia is the activation of a group of transcription factors of the HIF (Hypoxia-Inducible Factor) family, which include several isoforms and control the 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 the cellular response to hypoxia by influencing the activation of HIF, its degradation, and the translation of proteins dependent on it. At the same time, HIF also affects miRNA biogenesis. Data on the relationship of a particular HIF isoform with miRNA are contradictory, since studies are performed using different cell lines, different types of experimental animals and clinical material, as well as at different oxygen concentrations and different durations of hypoxic exposure. In addition, HIF expression may be affected by the initial resistance of organisms to lack of oxygen, which is not taken into account in studies. This review analyzes data on the effect of hypoxia on the biogenesis and functioning of miRNAs, as well as the effect of microRNAs on mRNAs of genes involved in adaptation to oxygen deficiency. Understanding the mechanisms of the relationship between HIF, hypoxia, and miRNA is necessary to develop new approaches to personalized therapy for diseases accompanied by oxygen deficiency.