Theranostics 2022; 12(13):5776-5802. doi:10.7150/thno.73931 This issue

Review

Emerging roles of extracellular vesicle-associated non-coding RNAs in hypoxia: Insights from cancer, myocardial infarction and ischemic stroke

Dirk M. Hermann1*✉, Wenqiang Xin2*, Mathias Bähr2, Bernd Giebel3, Thorsten R. Doeppner2,4,5,6✉

1. Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
2. Department of Neurology, University of Göttingen Medical School, Göttingen, Germany
3. Institute of Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
4. Research Institute for Health Sciences and Technologies (SABITA), Medipol University, Istanbul, Turkey
5. Department of Anatomy and Cell Biology, Medical University of Varna, Varna, Bulgaria
6. Department of Neurology, University of Giessen Medical School, Giessen, Germany
*Equal contribution.

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Citation:
Hermann DM, Xin W, Bähr M, Giebel B, Doeppner TR. Emerging roles of extracellular vesicle-associated non-coding RNAs in hypoxia: Insights from cancer, myocardial infarction and ischemic stroke. Theranostics 2022; 12(13):5776-5802. doi:10.7150/thno.73931. Available from https://www.thno.org/v12p5776.htm

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Abstract

Graphic abstract

Hypoxia is a central pathophysiological component in cancer, myocardial infarction and ischemic stroke, which represent the most common medical conditions resulting in long-term disability and death. Recent evidence suggests common signaling pathways in these diverse settings mediated by non-coding RNAs (ncRNAs), which are packaged in extracellular vesicles (EVs) protecting ncRNAs from degradation. EVs are a heterogeneous group of lipid bilayer-covered vesicles released from virtually all cells, which have important roles in intercellular communication. Recent studies pointed out that ncRNAs including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are selectively sorted into EVs, modulating specific aspects of cancer development, namely cell proliferation, migration, invasion, angiogenesis, immune tolerance or drug resistance, under conditions of hypoxia in recipient cells. In myocardial infarction and stroke, ncRNAs shuttled via EVs have been shown to control tissue survival and remodeling post-hypoxia by regulating cell injury, inflammatory responses, angiogenesis, neurogenesis or neuronal plasticity. This review discusses recent evidence on EV-associated ncRNAs in hypoxic cancer, myocardial infarction and stroke, discussing their cellular origin, biological function and disease significance. The emerging concept of lncRNA-circular RNA/ miRNA/ mRNA networks is outlined, upon which ncRNAs synergistically respond to hypoxia in order to modify disease responses. Particular notion is given to ncRNAs participating in at least two of the three conditions, which revealed a large degree of overlaps across pathophysiological conditions. Possible roles of EV-ncRNAs as therapeutic products or theranostic markers are defined.