MicroRNA-31-5p attenuates doxorubicin-induced cardiotoxicity via quaking and circular RNA Pan3

Ji, Xiaoyu; Ding, Wei; Xu, Tao; Zheng, Xianxin; Zhang, Jing; Liu, Mengxin; Liu, Gaoli; Jx, Wang

doi:10.1016/j.yjmcc.2020.02.009

Cited by 37 publications

(43 citation statements)

References 44 publications

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“…MicroRNAs (miRs) are endogenous, small, noncoding RNAs that modulate gene expression post-transcriptionally by binding to the 3′-untranslated region (3′-UTR) of target genes 14 . MiRs play important roles in the pathogenesis of various heart diseases, including coronary heart diseases, heart failure, and immune myocarditis 15 , 16 . In particular, numerous miRNAs take part in cardiotoxicity by modulating macrophage polarization 17 .…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling

et al. 2020

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Cancer immunotherapy has become a well-established treatment option for some cancers; however, its use is hampered by its cardiovascular adverse effects. Immune checkpoint inhibitors (ICIs)-related cardiac toxicity took place in kinds of different forms, such as myocarditis, acute coronary syndrome, and pericardial disease, with high mortality rates. This study aimed to investigate the roles of programmed death-1 (PD-1) inhibitor, one of widespread used ICIs, in the development of murine cardiac injury. PD-1 inhibitor is known to transduce immunoregulatory signals that modulate macrophages polarization to attack tumor cells. Hence, this study explored whether the cardiovascular adverse effects of PD-1 inhibitor were related to macrophage polarization. MicroRNA-34a (miR-34a), which appears to regulate the polarization of cultured macrophages to induce inflammation, is examined in cardiac injury and macrophage polarization induced by the PD-1 inhibitor. As a target of miR-34a, Krüppel-like factor 4 (KLF4) acted as an anti-inflammation effector to take cardiac protective effect. Further, it investigated whether modulating the miR-34a/KLF4-signaling pathway could influence macrophage polarization. The PD-1 inhibitor markedly induced M1 phenotype macrophage polarization with impaired cardiac function, whereas miR-34a inhibitor transfection treatment reversed M1 polarization and cardiac injury in vivo. In vitro, PD-1 inhibitor-induced M1 polarization was accompanied by an increase in the expression of miR-34a but a decrease in the expression of KLF4. TargetScan and luciferase assay showed that miR-34a targeted the KLF4 3′-untranslated region. Either miR-34a inhibition or KLF4 overexpression could abolish M1 polarization induced by the PD-1 inhibitor. The findings strongly suggested that the PD-1 inhibitor exerted its effect in promoting M1 polarization and cardiac injury by modulating the miR-34a/KLF4-signaling pathway and inducing myocardial inflammation. These findings might help us to understand the pathogenesis of cardiac injury during immunotherapy, and provide new targets in ameliorating cardiac injury in patients with cancer receiving PD-1 inhibitor treatment.

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Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling

et al. 2020

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“…Liu et al proved that miR-31-5p could repress the proliferation and differentiation of tongue myoblasts [ 42 ]. Results from Ji et al indicated that miR-31-5p silence significantly alleviated the doxorubicin-induced myocardial apoptosis and cardiac dysfunction in mice [ 43 ]. A very recent study by Toyonaga et al demonstrated that miR-31-5p was required for colonic epithelial cell integrity and could predict the clinical outcomes in patients with Crohn's disease [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-31-5p Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via Inactivating Cab39/AMPKα Pathway

Jiang

Zhao

Wen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome remain devastating diseases with high mortality rates and poor prognoses among patients in intensive care units. The present study is aimed at investigating the role and underlying mechanisms of microRNA-31-5p (miR-31-5p) on lipopolysaccharide- (LPS-) induced ALI. Mice were pretreated with miR-31-5p agomir, antagomir, and their negative controls at indicated doses for 3 consecutive days, and then they received a single intratracheal injection of LPS (5 mg/kg) for 12 h to induce ALI. MH-S murine alveolar macrophage cell lines were cultured to further verify the role of miR-31-5p in vitro. For AMP-activated protein kinase α (AMPKα) and calcium-binding protein 39 (Cab39) inhibition, compound C or lentiviral vectors were used in vivo and in vitro. We observed an upregulation of miR-31-5p in lung tissue upon LPS injection. miR-31-5p antagomir alleviated, while miR-31-5p agomir exacerbated LPS-induced inflammation, oxidative damage, and pulmonary dysfunction in vivo and in vitro. Mechanistically, miR-31-5p antagomir activated AMPKα to exert the protective effects that were abrogated by AMPKα inhibition. Further studies revealed that Cab39 was required for AMPKα activation and pulmonary protection by miR-31-5p antagomir. We provide the evidence that endogenous miR-31-5p is a key pathogenic factor for inflammation and oxidative damage during LPS-induced ALI, which is related to Cab39-dependent inhibition of AMPKα.

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“…MicroRNA-31-5p acts as a negative regulator of circPAN3 by directly suppressing QKI in doxorubicin-induced apoptosis of cardiomyocytes (117). circPAN3 also ameliorates myocardial ischemia and reperfusion injury by regulating miR-421/Pink1 axis-mediated suppression of autophagy (118).…”

Section: Circrna and Cvdsmentioning

confidence: 99%

Circular RNAs and Cardiovascular Regeneration

Tang

Jang

et al. 2021

Front. Cardiovasc. Med.

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circular RNAs (circRNAs) are a type of non-coding RNAs that are widely present in eukaryotic cells. They have the characteristics of stable structure, high abundance, and cell or tissue specific expression. circRNAs are single-stranded RNAs that are covalently back spliced to form closed circular loops. They may participate in gene expression and regulation through a variety of action modes. circRNAs can encode proteins or function by acting as miRNA sponges for protein translation. Since 2016, a growing number of research studies have shown that circRNAs play important role in the pathogenesis of cardiovascular disease. With the construction of circRNA database, the differential expression of circRNAs in the heart tissue samples from different species and the gradual elucidation of its mode of action in disease may become an ideal diagnosis biomarker and an effective therapeutic target. What can be expected surely has a broader application prospect. In this review, we summarize recent publications on circRNA biogenesis, expression profiles, functions, and the most recent studies of circRNAs in the field of cardiovascular diseases with special emphasis on cardiac regeneration.

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MicroRNA-31-5p attenuates doxorubicin-induced cardiotoxicity via quaking and circular RNA Pan3

Cited by 37 publications

References 44 publications

Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling

Immune checkpoint inhibitor induces cardiac injury through polarizing macrophages via modulating microRNA-34a/Kruppel-like factor 4 signaling

MicroRNA-31-5p Exacerbates Lipopolysaccharide-Induced Acute Lung Injury via Inactivating Cab39/AMPKα Pathway

Circular RNAs and Cardiovascular Regeneration

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