A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes

Bayoumi, Ahmed S.; Park, Kyoung Mi; Wang, Yongchao; Teoh, Jian Peng; Aonuma, Tatsuya; Tang, Yaoliang; Su, Huabo; Weintraub, Neal L.; Kim, Il-man

doi:10.1016/j.yjmcc.2017.11.003

Cited by 77 publications

(71 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MiR-125b-5p represses proapoptotic bak1 and klf13 in cardiomyocytes and protects the heart from AMI. 20) MiR-19a/19b could reduce MI-induced cardiac damage and protect cardiac function. 21) Despite the therapies of miRNAs in MI, there are still many miRNAs that act as a potential therapeutic target in MI.…”

Section: Discussionmentioning

confidence: 96%

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

et al. 2020

View full text Add to dashboard Cite

Myocardial infarction (MI) is one of the major causes of death worldwide, and the therapeutic strategies of MI are still limited. In this study, we investigated the function of miR-665 in MI. In the present study, an ischemia/reperfusion (I/R) rat model and a hypoxia/reoxygenation (H/R)-induced H9c2 cell model were successfully established to mimic the MI for in vivo and in vitro studies. The concentrations of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α), IL-6, and reactive oxygen species (ROS) were then measured. Moreover, cell viability and apoptosis were detected by MTT assay, TdT-mediated dUTP nick end labeling (TUNEL), and PI/FITC-annexin V assay. The binding of miR-665 and Pak1 was determined by luciferase assay. miR-665 was upregulated in I/R rats, and the overexpression of miR-665 significantly increased LDH, CK-MB, TNF-α, IL-6, and ROS concentrations and induced cell apoptosis, while knockdown of miR-665 had opposite results. Consistent with in vivo results, miR-665 induced cell apoptosis and ROS generation in H/R-treated H9c2 cells. More importantly, Pak1 was the target gene of miR-665, and knockdown of miR-665 depressed the accumulation of ROS and cell apoptosis by targeting Pak1 and promoting the phosphorylation of Akt, whereas knockdown of Pak1 could attenuate the protection of miR-665 inhibitor in H/ R-treated H9c2 cells. Therefore, knockdown of miR-665 protects against cardiomyocyte ischemia/reperfusion injury-induced ROS accumulation and apoptosis through activating Pak1/Akt signaling in MI. In general, understanding the biology and modulation of miR-665 may have the potential to counteract the development of MI.

show abstract

Section: Discussionmentioning

confidence: 96%

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It should be noted that miR-125b-5p acts as an ischemic stress protector after acute myocardial infarction, opposing cardiomyocyte apoptosis by repressing pro-apoptotic bak1 (a mitochondrial protein) and klf13 (a zinc finger transcription factor). 8 The increased expression of miR-125b significantly decreases infarct size and prevents I/R injury in the myocardium. 9 These reports may indicate that the specific temporal and spatial expression patterns of miR-125b-5p have different biological functions.…”

Section: Discussionmentioning

confidence: 99%

“…7 In addition, miR-125b-5p is involved in the acute response to myocardial I/R injury and myocardial infarction. 8,9 miR-15a is increased in the brain after I/R injury or transient ischemia. [10][11][12] Genetic deletion or pharmacological inhibition of the miR-15a/16-1 cluster significantly reduced I/R brain injury.…”

Section: Introductionmentioning

confidence: 99%

Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study

Shi

Zhao

et al. 2019

Journal of Stroke and Cerebrovascular Diseases

View full text Add to dashboard Cite

Introduction: Multiple microRNAs (miRNAs) participate in the response to hypoxic/ ischemic and ischemia-reperfusion events. However, the expression of these miRNAs in circulation from patients with acute ischemic stroke (AIS) receiving recanalization treatment has not been examined, and whether they are associated with the severity and outcome of stroke is still unknown. Materials and methods: In this prospective cohort study, plasma levels of miR-125b-5p, miR-15a-3p, miR-15a-5p, and miR-206 were measured at 24 hours after thrombolysis with or without endovascular treatment in 94 patients with AIS, as determined by qRT-PCR. Stroke severity was assessed based on National Institutes of Health Stroke Scale (NIHSS) score and infarct lesion. Intracranial haemorrhage (ICH) was recorded. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2 at day 90 after stroke. Results: miR-125b-5p and miR-206 levels were correlated with NIHSS scores (P = .014 and P = .002) and cerebral infarction volumes (P = .025 and P = .030). miR-125b-5p levels were significantly higher in patients with an unfavorable outcome than in patients with a favorable outcome (P = .002) and showed good diagnostic accuracy in discriminating the presence of an unfavorable outcome (area under the curve .735, 95% confidence interval .623-.829, P < .001). No association was found between different miRNAs and ICH. Conclusions: In AIS patients after thrombolysis with or without endovascular treatment, miR-125b-5p is a novel prognostic biomarker highly associated with an unfavorable outcome. miR-125b-5p and miR-206 levels are associated with stroke severity.

show abstract

“…It has been confirmed that NLRC5 participates in the transformation and invasion of malignant cancer cells (18,19) and an increasing number of studies have found that NLRC5 is associated with non-immunological diseases (20). MiR-125b-5p is a known regulator of apoptosis in several types of cells (21)(22)(23). Recently, NLRC5 was reported to have a protective effect against heart disease (24).…”

Section: Lncrna Malat1 Prevents the Protective Effects Of Mir-125b-5pmentioning

confidence: 99%

LncRNA MALAT1 prevents the protective effects of miR‑125b‑5p against acute myocardial infarction through positive regulation of NLRC5

Liu

Wei

et al. 2019

Exp Ther Med

View full text Add to dashboard Cite

Acute myocardial infarction (AMI), as the first manifestation of ischemic heart disease, is the most common cause of death in developed countries. A recent study showed that metastasis associated lung adenocarcinoma transcript 1 (MALAT1), a prognostic marker for lung cancer metastasis, could promote myocardial ischemia-reperfusion injury by regulating the levels of microRNA (miR)-145. In order to elucidate the biological function of MALAT1 in the pathogenesis of AMI and to explore the mechanisms underlying its action, an AMI rat model was established by ligation of the left anterior descending coronary artery. Downregulation of MALAT1 by siRNA transfection attenuated heart damage in an AMI model rat. The mouse cardiomyocyte cell line HL-1 was used to show that downregulation of nucleotide binding and oligomerization domain-like receptor C5 (NLRC5) and upregulation of miR-125b-5p were the results of MALAT1 silencing. TargetScan and a dual-luciferase reporter assay indicated that NLRC5 is a direct target of miR-125b-5p. Overexpression of miR-125b-5p significantly reduced hypoxia/reperfusion-induced apoptosis of HL-1 cells, an effect that could be blocked by NLCR5 overexpression. Taken together, these results suggest that MALAT1 reduced the protective effect of miR-125b-5p on injured cells through upregulation of NLCR5. This study highlights the role of MALAT1 in the pathogenesis of AMI and may guide future genetic therapeutic strategies for AMI treatment.

show abstract

A carvedilol-responsive microRNA, miR-125b-5p protects the heart from acute myocardial infarction by repressing pro-apoptotic bak1 and klf13 in cardiomyocytes

Abstract: In conclusion, these findings reveal a pivotal role for miR-125b-5p in regulating CM survival during acute myocardial infarction.

Cited by 77 publications

References 63 publications

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

Plasma Levels of miR-125b-5p and miR-206 in Acute Ischemic Stroke Patients After Recanalization Treatment: A Prospective Observational Study

LncRNA MALAT1 prevents the protective effects of miR‑125b‑5p against acute myocardial infarction through positive regulation of NLRC5

Contact Info

Product

Resources

About