MicroRNA-210: a unique and pleiotropic hypoxamir.
Inadequate oxygen availability or hypoxia induces a complex and still incompletely understood set of adaptations that influence cellular survival and function. Many of these adaptations are directly controlled by a master transcription factor, hypoxia inducible factor-alpha (HIF-α). In response to hypoxia, HIF-α levels increase and directly induce the transcription of > 100 genes, influencing functions ranging from metabolism, survival, proliferation, migration, to angiogenesis, among others. Recently, it has been demonstrated that a specific set of microRNA molecules are upregulated by hypoxia, which we denote here as "hypoxamirs." In particular, the HIF-responsive hypoxamir microRNA-210 (miR-210) is a unique microRNA that is evolutionarily conserved and ubiquitously expressed in hypoxic cell and tissue types. A number of direct targets of miR-210 have been identified by in silico, transcriptional, and biochemical methods, a subset of which have been extensively validated. As a result, miR-210 has been mechanistically linked to the control of a wide range of cellular responses known to influence normal developmental physiology as well as a number of hypoxia-dependent disease states, including tissue ischemia, inflammation, and tumorigenesis. Thus, reflecting the pleiotropic actions of HIF-α, miR-210 appears to function as a "master microRNA" relevant for the control of diverse functions in the hypoxic state.
Harvard Medical School; Boston, MA.
Stephen Y
SY
Chan
Joseph
J
Loscalzo
D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs