MicroRNA‐214 Protects Cardiac Myocytes Against H₂O₂‐Induced Injury

Abstract

Reactive oxygen species (ROS)-induced cardiac myocyte injury resulting from changes in the expression levels of multiple genes plays a critical role in the pathogenesis of numerous heart diseases. The purpose of this study was to determine the potential roles of microRNA-214 (miR-214) in hydrogen peroxide (H2O2)-mediated gene regulation in cardiac myocytes. In this study, we used quantitative real-time RT-PCR (qRT-PCR) to demonstrate that miR-214 was upregulated in cardiac myocytes after treatment with H2O2. We transfected cells with pre-miR-214 to upregulate miR-214 expression and transfected cells with a miR-214 inhibitor (anti-miR-214) to downregulate miR-214 expression. H2O2-induced cardiac cell apoptosis was detected by flow cytometry. The level of apoptosis was increased by the miR-214 inhibitor and decreased by pre-miR-214. Therefore, we believe that miR-214 plays a positive role in H2O2-induced cardiac cell apoptosis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is constitutively active and is considered to be the primary downregulator of the pro-oncogenic PI3K/Akt pathway. Western blot analysis revealed that the expression of the PTEN protein in cardiac myocytes decreased after H2O2 induction. Anti-miR-214 increased PTEN protein expression level, in contrast, pre-miR-214 decreased the PTEN protein expression level in cultured cardiac myocytes. These results indicate that PTEN is regulated by miR-214 and serves as an important target of miR-214 in cardiac myocytes. In conclusion, miR-214 is sensitive to H2O2 stimulation, and miR-214 protects cardiac myocytes against H2O2-induced injury via one of its targets, PTEN.

MicroRNA-214 Inhibits Left Ventricular Remodeling in an Acute Myocardial Infarction Rat Model by Suppressing Cellular Apoptosis via the Phosphatase and Tensin Homolog (PTEN)

“…This result suggests that miR-214 protects the heart by repressing cardiomyocyte apoptosis through inhibition of PTEN. Our previous study 19) has shown that PTEN is regulated by miR-214 and serves as an important target of miR-214 in cardiac myocytes. A similar study 20) showed that miR-214 protects the heart against I/R injury by blunting Ca 2+ overload and cell death in response to injury through its repression of NCX1, CaMKIIδ, CypD, and BIM.…”

MicroRNA-424 Protects Against Focal Cerebral Ischemia and Reperfusion Injury in Mice by Suppressing Oxidative Stress

“…MiRNAs are implicated in the cellular response to oxidative stress via several different mechanisms [24][25][26][27] ; of these, the antioxidant defense system is responsible for preventing ROS accumulation during cerebral I/R. Some miRNAs directly target antioxidant/oxidant genes; for instance, miR-34a induces apoptosis in the human glioma cell line via enhanced nicotinamide adenine dinucleotide phosphate oxidase 2 expression and ROS production, 24 whereas miR-155 modulates ROS level by targeting SH2-domain-containing inositol 5-phosphatases in macrophages.…”

“…МикроРНК участвуют в клеточном ответе на окси-дантный стресс посредством различных механизмов [24][25][26][27]; одним из них является система антиоксидант-ной защиты, отвечающая за предотвращение накоп-ления АФК во время церебральной И/Р. Некоторые микроРНК нацелены непосредственно на антиокси-дантные/оксидантные гены; например микроРНК-34а индуцирует апоптоз в линии клеток глиомы чело-века путем повышения экспрессии никотинамид аде ниндинуклеотидфосфатоксидазы-2 и образования АФК [24], в то время как микроРНК-155 модулирует содержание АФК посредством влияния на SH2-домен-содержащую инозитол 5-фосфатазу в макрофагах [25].…”

“…MiR-424 also blocked the increase in LDH leakage and MDA content caused by H 2 O 2 and improved cell viability and MnSOD activity of primary cortical neurons; these protective effects were inhibited by Nrf2 knockdown and SOD inhibitor treatment. Taken together, these results demonstrate that miR-424 reduces oxidative stress both in vivo and in vitro.MiRNAs are implicated in the cellular response to oxidative stress via several different mechanisms [24][25][26][27] ; of these, the antioxidant defense system is responsible for preventing ROS accumulation during cerebral I/R. Some miRNAs directly target antioxidant/oxidant genes; for instance, miR-34a induces apoptosis in the human glioma cell line via enhanced nicotinamide adenine dinucleotide phosphate oxidase 2 expression and ROS production, 24 whereas miR-155 modulates ROS level by targeting SH2-domain-containing inositol 5-phosphatases in macrophages.…”

Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers

“…A previous study also reported that miR-214 bound to the 3′-UTR of PTEN mRNA and facilitated the degradation of PTEN mRNA. 46) Thus, we investigated whether the decrease in the mRNA levels of HMG-CoAS, SQS, and PTEN was caused by an increase in miR-214 levels in the livers of SHRSP. No significant differences were observed in HMG-CoAS, SQS, or PTEN mRNA levels in the liver between SHRSP and WKY, although a slight decrease was noted in PTEN mRNA in SHRSP (Fig.…”