MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

Yang, Guoshuai; Song, Yue; Zhou, Xiaoyan; Deng, Yidong; Liu, Tao; Weng, Guohu; Yu, Dan; Pan, Suyue

doi:10.3892/mmr.2015.3728

Cited by 103 publications

(59 citation statements)

References 28 publications

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“…Altered expression of miR-29b has been detected in multiple tumors and leukemia [28,29], raising the intriguing possibility that aberrant miR-29b expression and/or function may be associated with dysfunction of the apoptosisrelated pathway. Recent studies have demonstrated that miR-29a and miR-29c are involved in neuronal apoptosis and the serum levels of these miRs are negatively correlated with Parkinson's disease severity [24,30,31]. Han et al reported that miR-29a regulated high glucose-induced myocardial cell apoptosis by targeting IGF-1 [32].…”

Section: Discussionmentioning

confidence: 99%

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

Jing

Yang²,

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Myocardial apoptosis plays an important role in doxorubicin (Dox) cardiotoxicity. MicroRNA-29 (miR-29) is suggested to function as an anti-fibrotic factor with potential therapeutic effects on cardiac fibrosis. However, it has not been shown whether there is an association between miR-29b and myocardial apoptosis. Methods: Male Wistar rats were transfected with miR-29b agomir by local delivery to the myocardium prior to Dox treatment. Rat cardiomyocytes were pretreated with miR-29b mimics or inhibitor followed by Dox incubation in vitro. Cardiac function and underlying mechanisms were evaluated by echocardiography, immunofluorescence, flow cytometry, real-time PCR, and western blotting. Results: Our results revealed that miR-29b is the only member of the miR-29 family that was significantly downregulated in myocardium from Dox-treated rats. Delivery of miR-29b agomir to myocardium resulted in a marked improvement of cardiac function. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed that rescue of miR-29b expression inhibited Dox-induced myocardial apoptosis, concomitantly with increased Bcl-2 expression and decreased Bax expression and caspase-3 activity. In vitro, miR-29b overexpression mitigated, whereas inhibition of miR-29b promoted, Dox-induced cardiomyocyte apoptosis. Mechanistically, miR-29b negatively regulated Bax expression by directly targeting the 3′ untranslated region of Bax. In Dox-treated cardiomyocytes, upregulation of miR-29b resulted in a significant decrease in Bax expression, with an increase in Bcl-2 expression, accompanied by inhibition of mitochondrial membrane depolarization, cytochrome c release, and caspase activation. However, inhibition of miR-29b produced the opposite effects by further augmenting the effects of Dox. Conclusions: These data demonstrate that miR-29b prevents Dox-induced myocardial apoptosis through inhibition of the mitochondria-dependent pathway by directly targeting Bax, suggesting that miR-29b is a potential novel therapeutic target for the treatment of Dox cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

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

Jing

Yang²,

Jiang

et al. 2018

Cell Physiol Biochem

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“…Yang and colleagues (2015) studied the expression levels of the miR-29 family in peripheral blood samples from patients with AD and age-matched controls [48]. They found a comparatively marked decrease in miR-29c expression and a significant increase in BACE1 expression in the samples from the AD patients.…”

Section: Bace1 and Micrornasmentioning

confidence: 99%

“…Yang and colleagues also investigated the role of miR-29 on hippocampal neurons in vitro and in vivo. They found miR-29c upregulation promoted learning and memory behaviors in SAMP8 mice by increasing the activity of the protein kinase A/cAMP response element-binding protein, which is involved in neuroprotection, suggesting that miR-29c may be a possible therapeutic target against AD [48]. …”

Section: Bace1 and Micrornasmentioning

confidence: 99%

A critical evaluation of neuroprotective and neurodegenerative MicroRNAs in Alzheimer's disease

Reddy

Tonk

Kumar

et al. 2017

Biochemical and Biophysical Research Communications

116

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Currently, 5.4 million Americans suffer from AD, and these numbers are expected to increase up to 16 million by 2050. Despite tremendous research efforts, we still do not have drugs or agents that can delay, or prevent AD and its progression, and we still do not have early detectable biomarkers for AD. Multiple cellular changes have been implicated in AD, including synaptic damage, mitochondrial damage, production and accumulation of Aβ and phosphorylated tau, inflammatory response, deficits in neurotransmitters, deregulation of the cell cycle, and hormonal imbalance. Research into AD has revealed that miRNAs are involved in each of these cellular changes and interfere with gene regulation and translation. Recent discoveries in molecular biology have also revealed that microRNAs play a major role in post-translational regulation of gene expression. The purpose of this article is to review research that has assessed neuroprotective and neurodegenerative characteristics of microRNAs in brain samples from AD transgenic mouse models and patients with AD.

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“…Yang et al revealed that miR-29c negatively mediates the expression of DNA methyltransferase 3, which contributes to neuronal proliferation, by regulating the expression of brain-derived neurotrophic factor (6). Furthermore, the dysfunction of certain miRs has been suggested to be involved in the development of AD (8)(9)(10). Denk et al investigated the expression profiling of 1,178 miRs in cerebrospinal fluid samples from patients with AD and normal controls, and discrimination analysis using a combination of miR-100, miR-103 and miR-375 was able to detect AD by positively classifying controls and AD cases with 96.4 and 95.5% accuracy, respectively (8).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-135b has a neuroprotective role via targeting of β-site APP-cleaving enzyme 1

Zhang

Xing

Guo

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. MicroRNAs (miRs) are a class of endogenous small non-coding RNAs that have been revealed to negatively mediate the expression of their target genes at the post-transcriptional level. Recently, particular miRs have demonstrated an involvement in the pathogenesis of Alzheimer's disease (AD). However, the specific role of miR-135b in AD has yet to be elucidated. The present study aimed to investigate the neuroprotective role of miR-135b, in addition to its underlying mechanism. Herein, reverse transcription-quantitative polymerase chain reaction was conducted to determine miR-135b expression levels in the peripheral blood samples of patients with AD and age-matched normal controls. The data of the present study revealed that the expression levels of miR-135b were significantly reduced in the peripheral blood of AD patients compared with normal controls (P<0.01). In vitro MTT analyses identified that the overexpression of miR-135b significantly enhanced the proliferation of hippocampal cells (P<0.01). Furthermore, in vivo analysis using a Y-maze test indicated that injection with miR-135b mimics into the third ventricle of anesthetized SAMP8 mice significantly enhanced their learning and memory capacities (P<0.01). Molecular mechanism investigations identified β-site APP-cleaving enzyme 1 (BACE1) as a direct target gene of miR-135b, and the latter was identified to negatively mediate the protein expression levels of BACE1 in hippocampal cells, in addition to hippocampal tissues, of SAMP8 mice. Based on the aforementioned findings, we propose that miR-135b has a neuroprotective role via direct targeting of BACE1 and, thus, may be used for the treatment of AD.

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MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo

Cited by 103 publications

References 28 publications

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

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

A critical evaluation of neuroprotective and neurodegenerative MicroRNAs in Alzheimer's disease

MicroRNA-135b has a neuroprotective role via targeting of β-site APP-cleaving enzyme 1

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