ROS-mediated bidirectional regulation of miRNA results in distinct pathologic heart conditions

Lee, Seahyoung; Lim, Soyeon; Ham, Ok Kyung; Lee, Seyeon; Lee, Chang Yeon; Park, Jun‐Hee; Lee, Jiyun; Seo, Ho Seong; Yun, Ina; Han, Sun Young; Cha, Min‐Ji; Choi, Eun Kyoung; Hwang, Ki‐Chul

doi:10.1016/j.bbrc.2015.07.160

Cited by 17 publications

(10 citation statements)

References 26 publications

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“…This association might be partially explained by its recently reported involvement in reactive oxygen species (ROS) generation and subsequent oxidative stress-induced cardiomyocyte apoptosis - one of the main mechanisms of DOX-induced cardiotoxicity [1, 29, 30]. Indeed, previous studies [29–33] have shown that miR-1 suppresses the expression of antioxidant genes in cardiomyocytes that might lead to an imbalance between oxidative stress and antioxidant activities and a subsequent apoptosis that might elevate the circulating level of miR-1.…”

Section: Discussionmentioning

confidence: 99%

Circulating miR-1 as a potential biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients

et al. 2016

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Cardiotoxicity is associated with the chronic use of doxorubicin leading to cardiomyopathy and heart failure. Identification of cardiotoxicity-specific miRNA biomarkers could provide clinicians with a valuable prognostic tool. The aim of the study was to evaluate circulating levels of miRNAs in breast cancer patients receiving doxorubicin treatment and to correlate with cardiac function. This is an ancillary study from “Carvedilol Effect on Chemotherapy-induced Cardiotoxicity” (CECCY trial), which included 56 female patients (49.9±3.3 years of age) from the placebo arm. Enrolled patients were treated with doxorubicin followed by taxanes. cTnI, LVEF, and miRNAs were measured periodically. Circulating levels of miR-1, -133b, -146a, and -423-5p increased during the treatment whereas miR-208a and -208b were undetectable. cTnI increased from 6.6±0.3 to 46.7±5.5 pg/mL (p<0.001), while overall LVEF tended to decrease from 65.3±0.5 to 63.8±0.9 (p=0.053) over 12 months. Ten patients (17.9%) developed cardiotoxicity showing a decrease in LVEF from 67.2±1.0 to 58.8±2.7 (p=0.005). miR-1 was associated with changes in LVEF (r=-0.531, p<0.001). In a ROC curve analysis miR-1 showed an AUC greater than cTnI to discriminate between patients who did and did not develop cardiotoxicity (AUC = 0.851 and 0.544, p= 0.0016). Our data suggest that circulating miR-1 might be a potential new biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Circulating miR-1 as a potential biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients

et al. 2016

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“…Recent studies revealed the important roles of miRNAs in cardiac remodeling by regulating specific protein synthesis (Espinoza‐Lewis and Wang, ). Among them, miR‐1 is highly expressed and served as a regulator of both cardiac hypertrophy and apoptosis (Lee et al, ). Zhao et al () reported that adult miR‐1‐2 knockout mice died from cardiac arrhythmia because of the elevated expression of the miR‐1 target Irx5, a transcription factor that regulates the expression of Kcnd2, a potassium channel important for normal cardiac repolarization.…”

Section: Discussionmentioning

confidence: 99%

“…MiR‐1 was postulated to target ion channels and gap junction proteins, such as reducing Cx43 expression, and regulate cardiomyocyte polarization and depolarization (Ai et al, ; Zhang et al, ). It also participates in the pathogenesis of some other cardiovascular disorders, such as exacerbating apoptosis by suppressing the expression of heat shock protein 60 (HSP60) and B‐cell lymphoma 2 (Bcl‐2) (Lee et al, ). Hence, miR‐1 is considered as a promising target to treat cardiac arrhythmia.…”

Section: Discussionmentioning

confidence: 99%

P38 MAPK/miR‐1 are involved in the protective effect of EGCG in high glucose‐induced Cx43 downregulation in neonatal rat cardiomyocytes

et al. 2016

Cell Biology International

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The remodeling of cardiac gap junctions contributes to various arrhythmias in a diabetic heart. We previously reported that Epigallocatechin-3-gallate (EGCG) attenuated connexin43 (Cx43) protein downregulation induced by high glucose (HG) in neonatal rat cardiomyocytes, but Cx43 mRNA expression was not affected. It indicated the possible mechanisms of post-transcriptional regulation, which still remains unclear. As microRNAs (miRNAs) regulate gene expression widely at post-transcriptional level, we measured miR-1/206 in cardiomyocytes treated with HG and EGCG by quantitative RT-PCR and investigated their relationship with signal transduction pathways. The results showed that HG induced miR-1/206 elevation by PKC MAPK pathway. Moreover, we tested the negative regulation effect of miR-1/206 on Cx43 protein by miRNAs transfection. EGCG, however, nearly abolished the HG-induced miR-1 augmentation via P38 MAPK pathway. Therefore, our study suggested that PKC-activated miR-1/206 expression might contribute to Cx43 downregulation in HG-treated cardiomyocytes, and EGCG conferred protective effect by inhibiting miR-1 elevation via P38 MAPK pathway.

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“…Finally, the amount of ROS is a determining factor to modulate expression of miRNAs and their target genes that are important effectors during pathogenesis. During cardiac hypertrophy or I/R, Lee et al [241] showed that varying the intensity and the frequency of ROS dosages resulted in differential expressions of miR-1 and in decreasing levels of its target, myocardin. In vivo, miR-1 overexpression attenuated TAC-induced cardiac hypertrophy, while its inhibition attenuated I/R-induced cardiac apoptosis.…”

Section: Mir-1/206 and Oxidative Stress In The Cardiac And Pulmonary mentioning

confidence: 99%

MicroRNA and ROS Crosstalk in Cardiac and Pulmonary Diseases

Climent

Viggiani

Lin

et al. 2020

IJMS

101

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Reactive oxygen species (ROS) affect many cellular functions and the proper redox balance between ROS and antioxidants contributes substantially to the physiological welfare of the cell. During pathological conditions, an altered redox equilibrium leads to increased production of ROS that in turn may cause oxidative damage. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level contributing to all major cellular processes, including oxidative stress and cell death. Several miRNAs are expressed in response to ROS to mediate oxidative stress. Conversely, oxidative stress may lead to the upregulation of miRNAs that control mechanisms to buffer the damage induced by ROS. This review focuses on the complex crosstalk between miRNAs and ROS in diseases of the cardiac (i.e., cardiac hypertrophy, heart failure, myocardial infarction, ischemia/reperfusion injury, diabetic cardiomyopathy) and pulmonary (i.e., idiopathic pulmonary fibrosis, acute lung injury/acute respiratory distress syndrome, asthma, chronic obstructive pulmonary disease, lung cancer) compartments. Of note, miR-34a, miR-144, miR-421, miR-129, miR-181c, miR-16, miR-31, miR-155, miR-21, and miR-1/206 were found to play a role during oxidative stress in both heart and lung pathologies. This review comprehensively summarizes current knowledge in the field.

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ROS-mediated bidirectional regulation of miRNA results in distinct pathologic heart conditions

Cited by 17 publications

References 26 publications

Circulating miR-1 as a potential biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients

Circulating miR-1 as a potential biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients

P38 MAPK/miR‐1 are involved in the protective effect of EGCG in high glucose‐induced Cx43 downregulation in neonatal rat cardiomyocytes

MicroRNA and ROS Crosstalk in Cardiac and Pulmonary Diseases

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