MicroRNA-34a modulates the Notch signaling pathway in mice with congenital heart disease and its role in heart development

Wu, Kai; Xiao, Qian‐Ru; Yu, Yang; Xu, Jiali; Zhang, Feng; Liu, Chaoming; Zhang, Zhaoming; Lu, Ying-Qi; Huang, Ning‐Ping

doi:10.1016/j.yjmcc.2017.11.015

Cited by 25 publications

(19 citation statements)

References 27 publications

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“…Further studies revealed that diabetic pregnant mice display significant changes in exosomal miRNA profiles compared to normal pregnant mice [73,74]. Additionally, significant differential expression of more than 100 circulating miRNAs, including miR-34a, miR-142-5p, miR-1275, miR-4666a-3p and miR-3664-3p, in the peripheral blood of pregnant women carrying a foetus with abnormal heart development compared to women with normal pregnancy has also been reported [57,75,76]. These differentially expressed miRNAs are functionally predicted to be involved in the regulation of foetal heart development by bioinformatics analysis [24,[75][76][77].…”

Section: Circulating and Exosomal-derived Mirnas In Pregnant Women Wimentioning

confidence: 86%

“…Additionally, significant differential expression of more than 100 circulating miRNAs, including miR-34a, miR-142-5p, miR-1275, miR-4666a-3p and miR-3664-3p, in the peripheral blood of pregnant women carrying a foetus with abnormal heart development compared to women with normal pregnancy has also been reported [57,75,76]. These differentially expressed miRNAs are functionally predicted to be involved in the regulation of foetal heart development by bioinformatics analysis [24,[75][76][77]. Therefore, these results confirm that circulatory exosomes or circulating miRNAs in pregnancy participate in the regulation of foetal heart development, providing new insight into CHD diagnosis, prevention and even treatment.…”

Section: Circulating and Exosomal-derived Mirnas In Pregnant Women Wimentioning

confidence: 96%

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Clinical application of exosomes and circulating microRNAs in the diagnosis of pregnancy complications and foetal abnormalities

Yang

Wang

et al. 2020

J Transl Med

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During pregnancy in humans, the physiology of the mother and foetus are finely regulated by many factors. Inappropriate regulation can result in pregnancy disorders, such as complications and foetal abnormalities. The early prediction or accurate diagnosis of related diseases is a concern of researchers. Liquid biopsy can be analysed for circulating cells, cell-free nucleic acids, and exosomes. Because exosomes can be detected in the peripheral blood of women in early pregnancy, these vesicles and their contents have become the focus of early prediction or diagnostic biomarker research on pregnancy complications and foetal developmental disorders. In this review, we focus on recent studies addressing the roles of peripheral blood exosomes and circulating miRNAs in pregnancy complications and in pregnancies with abnormal foetal developmental disorders, with particular attention paid to the potential application value of exosomes and circulating miRNAs as disease-specific biomarkers.

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Section: Circulating and Exosomal-derived Mirnas In Pregnant Women Wimentioning

confidence: 86%

Section: Circulating and Exosomal-derived Mirnas In Pregnant Women Wimentioning

confidence: 96%

Clinical application of exosomes and circulating microRNAs in the diagnosis of pregnancy complications and foetal abnormalities

Yang

Wang

et al. 2020

J Transl Med

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“…Its ligand, Dlk-1, is a critical factor in specification through asymmetric division [ 24 ]. Mouse studies by Wu et al found evidence that miR-34a is a repressive regulator to NOTCH1, while upregulating Jagged1, Hey2, and Hes [ 25 ]. A variant of miR-1-1 in mice is miR-1-2, and its deletion has been found to be lethal to approximately 50% of embryos, while around 20% of survivors have major cardiac defects.…”

Section: Mirnas In Cardiomyocytesmentioning

confidence: 99%

A MicroRNA Perspective on Cardiovascular Development and Diseases: An Update

Islas

Moreno-Cuevas

2018

IJMS

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In this review, we summarize the latest research pertaining to MicroRNAs (miRs) related to cardiovascular diseases. In today’s molecular age, the key clinical aspects of diagnosing and treating these type of diseases are crucial, and miRs play an important role. Therefore, we have made a thorough analysis discussing the most important candidate protagonists of many pathways relating to such conditions as atherosclerosis, heart failure, myocardial infarction, and congenital heart disorders. We approach miRs initially from the fundamental molecular aspects and look at their role in developmental pathways, as well as regulatory mechanisms dysregulated under specific cardiovascular conditions. By doing so, we can better understand their functional roles. Next, we look at therapeutic aspects, including delivery and inhibition techniques. We conclude that a personal approach for treatment is paramount, and so understanding miRs is strategic for cardiovascular health.

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“…MiRNAs are emerging as a novel treatment for cardiovascular diseases 9 – 11 and recently, several studies have investigated the role of miRNAs in DOXO-induced cardiotoxicity 12 , 13 . MiR-34a is involved in several cellular processes, such as apoptosis, senescence and energy metabolism 14 , 15 and is recognized as a key regulator in cardiac diseases and repair 16 – 20 . Current studies revealed increased miR-34a levels in tissue and plasma of different models of DOXO-induced cardiotoxicity 19 , 21 – 23 and in plasma of oncologic patients after anthracycline chemotherapy 22 , 24 , 25 .…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective effects of miR-34a silencing in a rat model of doxorubicin toxicity

Piegari

Cozzolino

Ciuffreda

et al. 2020

Sci Rep

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Cardiotoxicity remains a serious problem in anthracycline-treated oncologic patients. Therapeutic modulation of microRNA expression is emerging as a cardioprotective approach in several cardiovascular pathologies. MiR-34a increased in animals and patients exposed to anthracyclines and is involved in cardiac repair. In our previous study, we demonstrated beneficial effects of miR-34a silencing in rat cardiac cells exposed to doxorubicin (DOXO). The aim of the present work is to evaluate the potential cardioprotective properties of a specific antimiR-34a (Ant34a) in an experimental model of DOXO-induced cardiotoxicity. Results indicate that in our model systemic administration of Ant34a completely silences miR-34a myocardial expression and importantly attenuates DOXOinduced cardiac dysfunction. Ant34a systemic delivery in DOXO-treated rats triggers an upregulation of prosurvival miR-34a targets Bcl-2 and SIRT1 that mediate a reduction of DOXO-induced cardiac damage represented by myocardial apoptosis, senescence, fibrosis and inflammation. These findings suggest that miR-34a therapeutic inhibition may have clinical relevance to attenuate DOXO-induced toxicity in the heart of oncologic patients. The anthracycline doxorubicin (DOXO) is a very powerful antineoplastic drug whose clinical use is limited by cardiotoxicity, its main side effect that may occur both acutely and chronically, affecting the quality of life of otherwise successfully treated oncologic patients 1,2. Anthracycline cardiotoxicity begins with subclinical myocardial damage, progresses to an early asymptomatic deterioration in left ventricle (LV) ejection fraction (EF) and ends, if not properly treated, with a symptomatic and often intractable heart failure (HF). For what concerns myocardial function, diastolic dysfunction may represent a precocious manifestation of DOXO cardiotoxicity, associated with ventricular relaxation and chamber wall stiffness leading to an alteration of ventricular function that first involves diastole and then eventually affects systole 3-6. Given the growing successful of chemotherapy with the significant increase in cancer survival, the clinical significance of DOXO cardiotoxicity is by no means small 7. Therefore, there is a serious need of an efficacious cardioprotective strategy to prevent or reduce ventricular complications. MicroRNAs (miRNAs) are small noncoding RNAs that suppress protein expression through binding and silencing specific mRNAs. A single miRNA inhibits many different mRNAs simultaneously, thus allowing an amplification of biological responses. A fine manipulation of miRNA expression and function through systemic or local delivery of miRNA inhibitors (antimiRs) or mimics, has triggered the interest for miRNAs as innovative therapeutic targets 8,9. MiRNAs are emerging as a novel treatment for cardiovascular diseases 9-11 and recently, several studies have investigated the role of miRNAs in DOXO-induced cardiotoxicity 12,13. MiR-34a is involved in several cellular processes, such as apoptosis, senescence ...

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MicroRNA-34a modulates the Notch signaling pathway in mice with congenital heart disease and its role in heart development

Cited by 25 publications

References 27 publications

Clinical application of exosomes and circulating microRNAs in the diagnosis of pregnancy complications and foetal abnormalities

Clinical application of exosomes and circulating microRNAs in the diagnosis of pregnancy complications and foetal abnormalities

A MicroRNA Perspective on Cardiovascular Development and Diseases: An Update

Cardioprotective effects of miR-34a silencing in a rat model of doxorubicin toxicity

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