Impact of MicroRNAs in the Cellular Response to Hypoxia

Abstract

In mammalian cells, hypoxia, or inadequate oxygen availability, regulates the expression of a specific set of MicroRNAs (MiRNAs), termed "hypoxamiRs." Over the past 10 years, the appreciation of the importance of hypoxamiRs in regulating the cellular adaptation to hypoxia has grown dramatically. At the cellular level, each hypoxamiR, including the master hypoxamiR MiR-210, can simultaneously regulate expression of multiple target genes in order to fine-tune the adaptive response of cells to hypoxia. This review addresses the complex molecular regulation of MiRNAs in both physiological and pathological conditions of low oxygen adaptation and the multiple functions of hypoxamiRs in various hypoxia-associated biological processes, including apoptosis, survival, proliferation, angiogenesis, inflammation, and metabolism. From a clinical perspective, we also discuss the potential use of hypoxamiRs as new biomarkers and/or therapeutic targets in cancer and aging-associated diseases including cardiovascular and fibroproliferative disorders.

Keywords: Aging; Biomarker; Cancer; Cardiovascular diseases; Fibroproliferative disorders; Hypoxia; Metabolism; MicroRNA; Noncoding RNA; Therapeutic target; hypoxamiR.