Plk2 Regulated by miR-128 Induces Ischemia-Reperfusion Injury in Cardiac Cells

Abstract

Ischemia-reperfusion (I/R) injury occurs during cardiac surgery and is the major factor leading to heart dysfunction and heart failure. Our previous study showed that gene and micro-RNA expression profiles are altered in heart grafts with extended I/R injury. In this study, we, for the first time, demonstrated that I/R injury upregulates the expression of Polo-like kinase 2 (Plk2) but decreases miR-128 expression in heart cells both in vitro and in vivo. Silencing Plk2 using small interfering RNA (siRNA) protects cells from Antimycin A-induced cell apoptosis/death. Silencing Plk2 also decreases phosphorylated p65 expression but increases Angiopoietin 1 expression. In addition, Plk2 is negatively regulated by miR-128. miR-128 exerts a protective effect on cell apoptosis similar to Plk2 siRNA in response to I/R stress. Methylation inhibitor 5-azacytidine (5-AZ) increases the expression of miR-128 and subsequently reduces Plk2 expression and cell apoptosis. In conclusion, this study demonstrated that Plk2 regulated by miR-128 induces cell apoptosis/death in response to I/R stress through activation of the nuclear factor kB (NF-kB) signal pathway. miR-128 and Plk2 are new targets for preventing cardiac I/R injury or oxidative stress-mediated injury.

PLK2 protects retinal ganglion cells from oxidative stress by potentiating Nrf2 signaling via GSK‐3β

“…However, other studies have suggested that PLK2 has a proapoptotic function under certain conditions. [ 15,16,28 ] Therefore, PLK2 may exert discrepant functions to regulate cell survival and apoptosis in different cell types and conditions.…”

“…[ 15 ] Silencing of PLK2 attenuates ischemia/reperfusion injury in cardiac cells. [ 16 ] Notably, PLK2 acts as a critical modulator for oxidative stress. [ 17 ] PLK2 is capable of activating antioxidant pathways and promotes cell survival under conditions of oxidative stress.…”

Transcriptome Signatures Reveal Candidate Key Genes in the Peripheral Blood Mononuclear Cells of Patients With Coronary Artery Disease

“…Filamin A (FLNA) was involved in development of hypertension [148], but this gene may be responsible for progression of CAD. Enriched genes such as PHLDA1 [149], PLK2 [150], IER3 [151] and thymopoietin (TMPO) [152] were identi ed with development of ischemic cardiomyopathy, but these genes may be involved in progression of CAD. TOR1AIP1 was associated with heart failure [153].…”

Transcriptome signatures reveal candidate key genes in the peripheral blood mononuclear cells of patients with coronary artery disease and prediction of small drug molecules

“…Filamin A (FLNA) was involved in development of hypertension [153], but this gene might be responsible for progression of CAD. Genes such as PHLDA1 [154], PLK2 [155], IER3 [156] and thymopoietin (TMPO) [157] were identi ed with development of ischemic cardiomyopathy, but these genes might be involved in progression of CAD. TOR1AIP1 was associated with heart failure [158].…”