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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.

Mengqi Li,1,2,* Weihan Wang,1,2,* Lin Zhang,3,* Wenqiang Xin,1,2,* Yan Zhao,1,2 Linchun Huan,4 Jianjun Yu,4 Hao Zhang,1,2 Jianning Zhang,1,2 Shuyuan Yang,1,2 Degang Liang,5,* Weidong Yang,1,2,* Xinyu Yang1,2,* 1Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Key Laboratory of Post-Neurotrauma Neurorepair and Regeneration in Central Nervous System, Ministry of Education in China and Tianjin, Tianjin Neurological Institute, Tianjin, People’s Republic of China; 3Department of Neurosurgery, Linyi People’s Hospital, Shandong, People’s Republic of China; 4Department of Cardio-Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 5Department of Neurosurgery, Tianjin Fifth Central Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Purpose: Genetic factors play a vital role in intracranial aneurysm (IA) onset and development. Studying the relationship between IA and the Sox17 polymorphisms in diverse populations is essential for establishing credibility.Patients and methods: We collected blood samples derived from a total of 596 sporadic IA patients and 600 individual controls in several medical institutes in China. We used the Sequenom MassArray system for single nucleotide polymorphisms (SNPs) genotyping after DNA extraction. The SNPs data was tested and analyzed in PLINK (version 1.9). Multiple-testing was performed in PLINK to make the statistics more rigorous and accurate.Results: We found that the allelic G of rs1072737 (OR=1.303, genomic-control corrected P-value=0.001032) is a risk allele, while the allelic G of rs9298506 (OR=0.7253, genomic-control corrected P-value=0.01559) is a protective allele in Chinese Han people.Conclusion: The allelic G of rs1072737 is a risk factor for IA, while the allelic G of rs9298506 serves as a protective factor for IA in Chinese Han people. Keywords: intracranial aneurysm, Sox17, genetics, cerebral vascular disease &nbsp