MicroRNA-29b Regulates the Mitochondria-Dependent Apoptotic Pathway by Targeting Bax in Doxorubicin Cardiotoxicity

Jing, Xibo; Yang, Jin Ming; Jiang, Lu; Chen, Jianghong; Wang, Haiyan

doi:10.1159/000491896

Cited by 58 publications

(48 citation statements)

References 29 publications

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“…The MiR‐371 family can be used as the plasma biomarkers for monitoring undifferentiated and potentially malignant human pluripotent stem cells (Salvatori et al, ). Besides, some groups have reported that miR‐29b‐3p plays important roles in cell apoptosis, inflammation, and oxidative stress (Jing et al, ; H. Wang et al, ; Xing et al, ; Zhang et al, ). MiR‐29 can be used as a clinical marker of disease.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have revealed that miR‐29b plays important roles in a variety of diseases (Langsch et al, ; S. Zhou et al, ). This miRNA can prevent doxorubicin‐induced myocardial apoptosis by targeting BAX (Jing, Yang, Jiang, Chen, & Wang, ), inhibit high‐mobility group box 1/TLR4 signallling in liver fibrosis (Zhang et al, ), inhibit breast cancer via targeting the DNA modifying enzyme TET1 (H. Wang et al, ), and alleviate IgAN pathogenesis via targeting the cyclin‐dependent kinase 6 (Xing et al, ). However, there are no reports of the effects of miR‐29b‐3p on II/R injury.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

Dai

Zhang

Han

et al. 2019

British J Pharmacology

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Background and Purpose The microRNA miR‐29b‐3p shows important roles in regulating apoptosis and inflammation. However, its effects on intestinal ischaemia/reperfusion (II/R) injury have not been reported. Here we have investigated the functions of miR‐29b‐3p on II/R injury on order to find drug targets to treat the injury. Experimental Approach Two models ‐ in vitro hypoxia/reoxygenation (H/R) of IEC‐6 cells; in vivo, II/R injury in C57BL/6 mice were used. Western blotting and dual‐luciferase reporter assays were used and mimic and siRNA transfection tests were applied to assess the effects of miR‐29b‐3p on II/R injury via targeting TNF receptor‐associated factor 3 (TRAF3). Key Results The H/R procedure decreased cell viability and promoted inflammation and apoptosis in IEC‐6 cells, and the II/R procedure also promoted intestinal inflammation and apoptosis in mice. Expression levels of miR‐29b‐3p were decreased in H/R‐induced cells and II/R‐induced intestinal tissues of mice compared with control group or sham group, which directly targeted TRAF3. Decreased miR‐29b‐3p level markedly increased TRAF3 expression via activating TGF‐α‐activated kinase 1 phosphorylation, increasing NF‐κB (p65) levels to promote inflammation, up‐regulating Bcl2‐associated X expression, and down‐regulating Bcl‐2 expression to trigger apoptosis. In addition, the miR‐29b‐3p mimetic and TRAF3 siRNA in IEC‐6 cells markedly suppressed apoptosis and inflammation to alleviate II/R injury via inhibiting TRAF3 signallimg. Conclusions and Implications The miR‐29b‐3p played a critical role in II/R injury, via targeting TRAF3, which should be considered as a significant drug target to treat the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

Dai

Zhang

Han

et al. 2019

British J Pharmacology

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“…Rescue of miR-29b expression in the myocardium resulted in a marked improvement of cardiac function. miR-29b overexpression in rat cardiomyocytes decreased DOX-induced cardiomyocyte apoptosis, since miR-29b targets directly the anti-apoptotic protein Bax [118].…”

Section: Mir-29 Familymentioning

confidence: 94%

“…It was shown that this family is modulated by different anti-cancer treatments. miR-29b is the member of the miR-29 family that was significantly downregulated in myocardium of DOX-treated rats [118]. Rescue of miR-29b expression in the myocardium resulted in a marked improvement of cardiac function.…”

Section: Mir-29 Familymentioning

confidence: 99%

MicroRNAs in Cancer Treatment-Induced Cardiotoxicity

Pellegrini

Sileno

D'agostino

et al. 2020

Cancers

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Cancer treatment has made significant progress in the cure of different types of tumors. Nevertheless, its clinical use is limited by unwanted cardiotoxicity. Aside from the conventional chemotherapy approaches, even the most newly developed, i.e., molecularly targeted therapy and immunotherapy, exhibit a similar frequency and severity of toxicities that range from subclinical ventricular dysfunction to severe cardiomyopathy and, ultimately, congestive heart failure. Specific mechanisms leading to cardiotoxicity still remain to be elucidated. For instance, oxidative stress and DNA damage are considered key players in mediating cardiotoxicity in different treatments. microRNAs (miRNAs) act as key regulators in cell proliferation, cell death, apoptosis, and cell differentiation. Their dysregulation has been associated with adverse cardiac remodeling and toxicity. This review provides an overview of the cardiotoxicity induced by different oncologic treatments and potential miRNAs involved in this effect that could be used as possible therapeutic targets.Cancers 2020, 12, 704 2 of 24 circulating miRNAs have been used as excellent biomarkers in different studies and can be used as biomarkers for cardiovascular diseases (CVDs) [5]. Moreover, miRNA deregulation is often associated with tumor progression, and many anticancer treatments affect miRNA expression. In this review we aimed to discuss relevant miRNAs modulated by therapies for cancer that have been demonstrated to be involved in CVD. In the following paragraphs, we provide an overview of the most important anticancer treatments that are known to induce cardiotoxicity. Anticancer Treatment and CardiotoxicityAnticancer treatment has accomplished remarkable progress in the last century resulting in improved quality of life and survival rates of cancer patients. These advances in cancer treatment, however, have been often accompanied by therapy-related complications, including secondary side effects on the whole organism [6].The most commonly used cancer therapeutics in modern medicine include the traditional surgery, radiotherapy, and conventional chemotherapy approaches; moreover, two new therapeutic modalities have been introduced in recent decades, namely molecularly targeted therapy and immunotherapy [7], as summarized in Figure 1. Traditional chemotherapy agents consist of non-specific cytotoxic treatments (e.g., alkylating agents and antimetabolites) that rapidly eliminate replicating cells, including not only tumor cells but also normal tissue cells, with a broad range of side effects that significantly limit their applications in cancer therapy. In contrast to conventional systemic chemotherapy, molecularly targeted cancer therapies, using novel drugs aimed at the inhibition of intracellular signaling pathways fundamental for cancer proliferation or differentiation (e.g., monoclonal antibodies and low molecular weight protein-kinase inhibitors), are thought to be cancer-specific, with fewer associated adverse effects on normal cells [8]. Lastly, immunother...

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“…MicroRNAs (miRNAs) are a class of noncoding RNAs about 22 nucleotides in length, which are reported to posttranscriptionally regulate target gene expression by directly binding to 3 ′ -untranslated regions (3 ′ -UTR) of target messenger RNAs [6]. It has been well recognized that a large number of miRNAs participate in regulating doxorubicininduced cardiotoxicity; thus, they could be used as potential cardiotoxicity biomarkers [7].…”

Section: Introductionmentioning

confidence: 99%

Dexrazoxane Protects Cardiomyocyte from Doxorubicin-Induced Apoptosis by Modulating miR-17-5p

Ruan

Shen

et al. 2020

BioMed Research International

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The usage of doxorubicin is hampered by its life-threatening cardiotoxicity in clinical practice. Dexrazoxane is the only cardioprotective medicine approved by the FDA for preventing doxorubicin-induced cardiac toxicity. Nevertheless, the mechanism of dexrazoxane is incompletely understood. The aim of our study is to investigate the possible molecular mechanism of dexrazoxane against doxorubicin-induced cardiotoxicity. We established a doxorubicin-induced mouse and cardiomyocyte injury model. Male C57BL/6J mice were randomly distributed into a control group (Con), a doxorubicin treatment group (DOX), a doxorubicin plus dexrazoxane treatment group (DOX+DEX), and a dexrazoxane treatment group (DEX). Echocardiography and histology analyses were performed to evaluate heart function and structure. DNA laddering, qRT-PCR, and Western blot were performed on DOX-treated cardiomyocytes with/without DEX treatment in vitro. Cardiomyocytes were then transfected with miR-17-5p mimics or inhibitors in order to analyze its downstream target. Our results demonstrated that dexrazoxane has a potent effect on preventing cardiac injury induced by doxorubicin in vivo and in vitro by reducing cardiomyocyte apoptosis. MicroRNA plays an important role in cardiovascular diseases. Our data revealed that dexrazoxane could upregulate the expression of miR-17-5p, which plays a cytoprotective role in response to hypoxia by regulating cell apoptosis. Furthermore, the miRNA and protein analysis revealed that miR-17-5p significantly attenuated phosphatase and tensin homolog (PTEN) expression in cardiomyocytes exposed to doxorubicin. Taken together, dexrazoxane might exert a cardioprotective effect against doxorubicin-induced cardiomyocyte apoptosis by regulating the expression of miR-17-5p/PTEN cascade.

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MicroRNA-29b Regulates the Mitochondria-Dependent Apoptotic Pathway by Targeting Bax in Doxorubicin Cardiotoxicity

Cited by 58 publications

References 29 publications

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

MicroRNAs in Cancer Treatment-Induced Cardiotoxicity

Dexrazoxane Protects Cardiomyocyte from Doxorubicin-Induced Apoptosis by Modulating miR-17-5p

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