MicroRNA-451 protects against cardiomyocyte anoxia/reoxygenation injury by inhibiting high mobility group box 1 expression.

Molecular medicine reports

PubMedID: 27121079

Xie J, Hu X, Yi C, Hu G, Zhou X, Jiang H. MicroRNA-451 protects against cardiomyocyte anoxia/reoxygenation injury by inhibiting high mobility group box 1 expression. Mol Med Rep. 2016;.
High mobility group box 1 (HMGB1) protein serves an important role in myocardial ischemia/reperfusion (I/R) injury. MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate numerous signaling pathways involved in myocardial I/R injury. The present study aimed to investigate whether miR-451 protects against cardiomyocyte anoxia/reoxygenation (A/R) injury by attenuating HMGB1 expression. Neonatal rat ventricular cardiomyocytes were prepared and then subjected to A/R injury. The effect of upregulation or downregulation of miR-451 on cell viability, apoptosis, superoxide dismutase (SOD) activity, and the expression of cleaved-caspase-3 and HMGB1 were measured accordingly. A luciferase assay was performed to further confirm whether miR-451 can directly recognize the 3'-untranslated region of HMGB1 in HEK293 cells. The expression of miR-451 was significantly decreased in the cardiomyocytes during A/R, and upregulation of miR-451 led to increased miR-451 expression (P<0. 05). Upregulation of miR-451 significantly attenuated the loss of cardiomyocyte viability (P<0. 05) and increased the intracellular levels of SOD during A/R (P<0. 05). Furthermore, upregulation of miR-451 significantly decreased the apoptosis of cardiomyocytes during A/R (P<0. 05). The HMGB1 mRNA and protein expression levels were significantly downregulated in the Ad-miR-451 group compared with those in the A/R group (P<0. 05). In addition, upregulation of miR-451 reduced its translocation from the nucleus to the cytoplasm. The luciferase assay confirmed that HMGB1 mRNA is a direct target of miR-451 in cardiomyocytes. In conclusion, the present study suggested that upregulation of miR-451 could protect against A/R-induced cardiomyocyte injury by inhibiting HMGB1 expression.