Abstract
Hypoxia influences different cellular biological processes. To reveal the dynamics of hypoxia's effects on miRNA regulation in vivo, we examined the expression levels of all miRNAs in human brain and heart specimens from cases of mechanical asphyxia compared with those from cases of craniocerebral injury and hemorrhagic shock. We further validated differently expressed miRNAs in another 84 human specimens and rat models. We found that mir-122 was significantly down-regulated and that its putative targets G6PC3, ALDOA and CS were increased in the brain and cardiac tissues in cases of mechanical asphyxia compared with craniocerebral injury and hemorrhagic shock. Our data indicate that mir-122 and its targets G6PC3, ALDOA and CS play roles in the hypoxia responses that regulate glucose and energy metabolism and can serve as hypoxia biomarkers.
Highlights
Hypoxia generally refers to insufficient oxygen supply to tissues that ranges from < 0.01% to 5%, and its duration can be chronic, acute or fluctuating
48 and 23 miRNAs differed in expression between the brain specimens of those who died of mechanical asphyxia
We found that the mRNA levels of all three genes were significantly increased in the mechanical asphyxia specimens compared with the specimens from craniocerebral injury and hemorrhagic shock using the same set of 48 brain and 36 cardiac specimens described above (Figure 5A and 5B)
Summary
Hypoxia generally refers to insufficient oxygen supply to tissues that ranges from < 0.01% to 5%, and its duration can be chronic, acute or fluctuating. We reported reversed expression patterns of three predicted mir-122 target genes, G6PC3, ALDOA and CS, which encode metabolic enzymes, in the corresponding human specimens. These findings were confirmed in a rat hypoxia model. Compared with those who died from craniocerebral injury and hemorrhagic shock, respectively Among these miRNAs, 10 out of 48 and 10 out of 23 were up-regulated by more than 2-fold, and others were down-regulated in the brain specimens that underwent mechanical asphyxia (Figure 1A, 1B and Table 1). Eight miRNAs (mir-31, mir-122, mir-219-2-3p, etc.) in the brain specimens and sixteen miRNAs (mir-192, mir148a, mir-122, etc.) in the cardiac specimens exhibited consistent changes as a result of mechanical asphyxia death compared with the other two causes of death (Table 1)
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