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J Cell Biochem. 2018 Feb;119(2):1429-1440. doi: 10.1002/jcb.26304. Epub 2017 Oct 5.

Knockdown of long non-coding RNA MEG3 protects H9c2 cells from hypoxia-induced injury by targeting microRNA-183.

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Department of Cardiovascular Internal Medicine, China-Japan Union Hospital of Jilin University, Changchun, China.
Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.


Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time, and ischemia is primarily caused due to hypoxia. This study evaluated the effects of long non-coding RNA maternally expressed gene 3 (MEG3) on hypoxic rat cardiomyocyte-drived H9c2 cells. Hypoxic injury was confirmed by alterations of cell viability, migration, invasion, apoptosis, and hypoxia-inducible factor 1α (HIF-1α) expression. MEG3 level in hypoxic cells and effects of its knockdown on hypoxic cells were assessed. The interactions between MEG3 and miR-183 as well as miR-183 and p27 were investigated. In addition, the effects of aberrantly expressed MEG3, miR-183, and p27 on hypoxic cells along with the activation of PI3K/AKT/FOXO3a signaling pathway were all assessed. Results showed that hypoxia induced decreases of cell viability, migration and invasion, and increases of apoptosis and expressions of HIF-1α and MEG3. Knockdown of MEG3 decreased hypoxia-induced injury in H9c2 cells. Knockdown of MEG3 also increased miR-183 expression, which was identified as a target of MEG3. The effects of MEG3 knockdown on the hypoxic cells were reversed by miR-183 silence. p27 was identified as a target gene of miR-183, and its expression negatively regulated by miR-183. The mechanistic studies revealed that knockdown of p27 decreased hypoxia-induced H9c2 cell injury by activating PI3K/AKT/FOXO3a signal pathways. These findings suggest that knockdown of MEG3 alleviates hypoxia-induced H9c2 cell injury by miR-183-mediated suppression of p27 through activation of PI3K/AKT/FOXO3a signaling pathway.


MEG3; acute myocardial infarction; hypoxia; microRNA-183; p27

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