Invited review: decoding the microRNA response to hypoxia

Abstract

microRNAs (miRNAs) were discovered nearly two decades ago by researchers who sought to understand how basic developmental mechanisms work in the nematode Caenorhabditis elegans. Since the identification of conserved miRNA families in higher eukaryotes, there has been an explosion of interest into how these tiny RNA molecules function. miRNAs are 20-24 nucleotide non-coding RNA molecules that predominantly regulate transcripts of target genes through translational inhibition. Much recent interest has focused on the influence of miRNAs on homeostatic regulation, and in particular, hypoxic responses. The ability to sense and respond to hypoxia is of fundamental importance to aerobic organisms and dysregulated oxygen homeostasis is a hallmark in the pathophysiology of cancer, neurological dysfunction, myocardial infarction, and lung disease. miRNAs are ideal mediators of hypoxic stress responses as they are able to modify gene expression both rapidly and reversibly. This enables miRNA-mediated gene regulatory circuits to modify metabolic networks with immaculate precision and control. Therefore, one may consider miRNAs as molecular rheostats which effect tuning and switching of regulatory circuits to facilitate survival and adaptation to hypoxic conditions. Such miRNA-mediated regulatory circuits would provide flexible and conditional alternatives to "conventional" transcriptional regulation. Here, I review recent discoveries that have boosted our understanding of miRNA regulation of hypoxia and discuss where future breakthroughs in this area may be made.

Ion channels/transporters as epigenetic regulators? —a microRNA perspective

“…For example, the ability to sense and respond to hypoxia is of fundamental importance to aerobic organisms, whereas dysregulated oxygen homeostasis is a hallmark in the pathophysiology of cancer, neurological dysfunction, myocardial infarction, and lung disease [17]. Since 2006, a multitude of reports have demonstrated that specific miRNAs are involved in hypoxic response and contribute to the repression of biologically important genes by low oxygen tension from a variety of different organisms, cell types, and disease states [1821].…”

Neuroprotective effects of microRNA-210 against oxygen-glucose deprivation through inhibition of apoptosis in PC12 cells

“…Hypoxia inducible factor-1α (HIF-1α) (13-18) is a transcription factor that is crucial for normal brain development and in the development of injuries. MicroRNAs (miRs), small (18-25 nts), non-coding RNAs that regulate gene expression by blocking the translation of target mRNAs or by accelerating their degradation, have recently been reported to be induced by hypoxia (19). In particular, miR-210, which is activated by HIF-1α (20), is a unique miR that has been evolutionarily conserved and ubiquitously expressed in hypoxic cell and tissue types (21)(22)(23)(24)(25)(26)(27).…”

Glucose Induces Sensitivity to Oxygen Deprivation and Modulates Insulin/IGF-1 Signaling and Lipid Biosynthesis inCaenorhabditis elegans

“…elegans has evolved the ability to survive low-oxygen environments and has therefore been utilized as a genetic model system to understand molecular responses to oxygen deprivation (Gray et al 2004;Powell-Coffman 2010;Padilla et al 2011;Pocock 2011;Ma et al 2013). C. elegans survive severe oxygen deprivation (1 day of anoxia, ,0.001 kPa O 2 , standard OP50 Escherichia coli diet, 20°) by entering into a hypometabolic state referred to as suspended animation.…”