MicroRNA-92a Inhibition Attenuates Hypoxia/Reoxygenation-Induced Myocardiocyte Apoptosis by Targeting Smad7

Zhang, Busheng; Zhou, Mi; Li, Canbo; Zhou, Jingxin; Li, Haiqing; Zhu, Dan; Wang, Zhe; Chen, Anqing; Zhao, Qiang

doi:10.1371/journal.pone.0100298

Cited by 59 publications

(49 citation statements)

References 33 publications

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“…A series of in vitro cell experiments were performed to verify the function of miR-182 in the progression of malignant progression of LSCC and how it plays a role in tumor suppressor genes. Inhibition of miRNA expressions by over-expressions or silencing is used to study the mechanism of action of the corresponding miRNA in malignant tumors [25,26]. Mimics and inhibitors can more effectively up-regulate and down-regulate the expressions of miRNA [27,28].…”

Section: Discussionmentioning

confidence: 99%

MiR-182 regulates cell proliferation and apoptosis in laryngeal squamous cell carcinoma by targeting the CRR9

et al. 2019

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Correspondence: Hongxia Deng (msrqvbo5805551@126.com) Background: The effect of miR-182 on the expressions of CRR9 in laryngeal squamous cell carcinoma (LSCC) cells, and the impact on invasion and metastasis of LSCC were investigated in the present paper. Methods: The expressions of miR-182 in LSCC tissue and cell line were detected by RT-qPCR. MTT assay and Annexin V staining were used to detect the effects of miR-182 on tumor cells proliferation. Target gene prediction and screening, and luciferase reporter assay were designed to verify downstream target genes of miR-182. The mRNA and protein expressions of CRR9 were detected by qRT-PCR and Western blot. Finally, the expressions of CRR9 were measured by transfecting cells with miR-182 in mice. Results: Compared with normal tissue and cell, the expressions of miR-182 in tumor tissues and cells were much lower. Over-expressions of miR-182 can increase apoptosis rate. Luciferase reporter assay revealed that CRR9 was a downstream gene of miR-182. Reintroduction of CRR9 abolished miR-182-induced LSCC cell growth inhibition. In animal models, over-expressions of miR-182 can reduce tumor weight and promote apoptosis. Conclusion: miR-182 can inhibit the proliferation of LSCC cells by directly inhibiting the expressions of CRR9, thereby suppressing the occurrences and developments of LSCC.

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Section: Discussionmentioning

confidence: 99%

MiR-182 regulates cell proliferation and apoptosis in laryngeal squamous cell carcinoma by targeting the CRR9

et al. 2019

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“…Our findings are consistent with previous studies performed in H9c2 cells. 13 Using an established murine model of MI, we then determined via quantitative real time PCR (RT-qPCR) that miR-92a was significantly upregulated in cardiomyocytes, fibroblasts, and in cardiomyocyte-derived exosomes following MI ( Figure 1B, C, D). We also proved that miR-92a was contained in cardiomyocyte-derived exosomes ( Figure 1D-F); to verify that mir-92a was actually confined inside exosomes, we treated the samples with RNase, showing that miRNA levels were not affected by RNase treatment, unless when in presence of the detergent Triton X-100 ( Figure 1F).…”

Section: Ischemic Injury Upregulates Mir-92a In Cardiac Myofibroblastsmentioning

confidence: 99%

Cardiomyocyte‐derived exosomal microRNA‐92a mediates post‐ischemic myofibroblast activation both in vitro and ex vivo

et al. 2020

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Aims We hypothesize that specific microRNAs (miRNAs) within cardiomyocyte‐derived exosomes play a pivotal role in the phenoconversion of cardiac myofibroblasts following myocardial infarction (MI). Methods and results We used an established murine model of MI, obtained in vivo via ligation of the left anterior descending coronary artery. We isolated adult cardiomyocytes and fibroblasts, and we assessed the functional role of cardiomyocyte‐derived exosomes and their molecular cargo in the activation of cardiac fibroblasts. We identified and biologically validated miR‐92a as a transcriptional regulator of mothers against DPP homologues 7 (SMAD7), a known inhibitor of α‐smooth muscle actin (α‐SMA), established marker of myofibroblast activation. We found that miR‐92a was significantly (P < 0.05) upregulated in cardiomyocyte‐derived exosomes and in fibroblasts isolated after MI compared with SHAM conditions (n ≥ 6/group). We tested the activation of myofibroblasts by measuring the expression levels of αSMA, periostin, and collagen. Primary isolated cardiac fibroblasts were activated both when incubated with cardiomyocyte‐derived exosomes isolated from ischemic cardiomyocytes and when cultured in conditioned medium of post‐MI cardiomyocytes, whereas no significant difference was observed following incubation with exosomes or medium from sham cardiomyocytes. These effects were attenuated when an inhibitor of exosome secretion, GW4869 (10 μM for 12 h) was included in the experimental setting. Through means of specific miR‐92a mimic and miR‐92a inhibitor, we also verified the mechanistic contribution of miR‐92a to the activation of cardiac fibroblasts. Conclusions Our results indicate for the first time that miR‐92a is transferred to fibroblasts in form of exosomal cargo and is critical for cardiac myofibroblast activation.

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“…In contrast, the hypoxia inducible expression of miR-200c, miR-92a, and miR-27a promotes cardiomyocyte cell death by targeting GATA-4, Smad 7, and interleukin 10 (IL-10) pathway, respectively [93–95]. GATA4 is a transcription factor required for the cardiomyocyte growth and survival and downregulation of miR-200c promotes GATA-4 dependent expression of antiapoptotic genes such as Bcl2 [93], while inhibition of hypoxia induced increase of miR-92a promotes translation of SMAD7 and blocking NF-kB p65 signaling [94]. miR-138 inhibits expression of Lcn2, a proapoptotic gene by abrogating MLK3/JNK/c-jun signaling pathway [96, 97].…”

Section: Mirna and Cardiomyocytes Injurymentioning

confidence: 99%

MicroRNA as a Therapeutic Target in Cardiac Remodeling

Chen

Ponnusamy

Liu

et al. 2017

BioMed Research International

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MicroRNAs (miRNAs) are small RNA molecules that contain 18–25 nucleotides. The alterations in their expression level play crucial role in the development of many disorders including heart diseases. Myocardial remodeling is the final pathological consequence of a variety of myocardial diseases. miRNAs have central role in regulating pathogenesis of myocardial remodeling by modulating cardiac hypertrophy, cardiomyocytes injury, cardiac fibrosis, angiogenesis, and inflammatory response through multiple mechanisms. The balancing and tight regulation of different miRNAs is a key to drive the cellular events towards functional recovery and any fall in this leads to detrimental effect on cardiac function following various insults. In this review, we discuss the impact of alterations of miRNAs expression on cardiac hypertrophy, cardiomyocytes injury, cardiac fibrosis, angiogenesis, and inflammatory response. We have also described the targets (receptors, signaling molecules, transcription factors, etc.) of miRNAs on which they act to promote or attenuate cardiac remodeling processes in different type cells of cardiac tissues.

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MicroRNA-92a Inhibition Attenuates Hypoxia/Reoxygenation-Induced Myocardiocyte Apoptosis by Targeting Smad7

Cited by 59 publications

References 33 publications

MiR-182 regulates cell proliferation and apoptosis in laryngeal squamous cell carcinoma by targeting the CRR9

MiR-182 regulates cell proliferation and apoptosis in laryngeal squamous cell carcinoma by targeting the CRR9

Cardiomyocyte‐derived exosomal microRNA‐92a mediates post‐ischemic myofibroblast activation both in vitro and ex vivo

MicroRNA as a Therapeutic Target in Cardiac Remodeling

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