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

Abstract

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.

• Authors: Jing Xie, Xiaorong Hu, Chunfeng Yi, Gangying Hu, Xiaoya Zhou, Hong Jiang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 13 Issue 6 Pg. 5335-41 (Jun 2016) ISSN: 1791-3004 [Electronic] Greece
• PMID: 27121079 (Publication Type: Journal Article)

Chemical References

• HMGB1 Protein
• Hbp1 protein, rat
• MIRN451A microRNA, rat
• MicroRNAs

Topics

• Animals
• Gene Expression Regulation
• HEK293 Cells
• HMGB1 Protein (biosynthesis)
• Humans
• MicroRNAs (metabolism)
• Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
• Myocytes, Cardiac (metabolism, pathology)
• Rats