Circular noncoding RNAs as potential therapies and circulating biomarkers for cardiovascular diseases

Bayoumi, Ahmed S.; Aonuma, Tatsuya; Teoh, Jian Peng; Tang, Yaoliang; Kim, Il-man

doi:10.1038/aps.2017.196

Cited by 87 publications

(73 citation statements)

References 81 publications

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“…In addition, circRNAs are more stable and abundant than miRNAs in serum and other body fluids, and in extracellular vesicles (13). Therefore, circRNAs are ideal candidates as potential disease biomarkers and therapeutic targets (14). However, the mechanisms underlying the roles of circRNAs in cardiomyocyte death induced by anoxia/reoxygenation (A/R) or ischemia/reperfusion (I/R) injury are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let‑7a‑5p/IGF2BP3 in cardiomyocytes

et al. 2019

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circular RNAs (circRNAs) serve important roles in cardiovascular diseases, including myocardial infarction. However, the mechanisms underlying the roles of circRNAs in cardiomyocyte death induced by anoxia/reoxygenation (A/R) are not fully understood. In the present study, the roles of circRNA_101237 and let-7a-5p in cardiomyocyte death induced by A/R injury were investigated. It was identified that circRNA_101237 was induced by A/R injury in a time-dependent manner and that circRNA_101237 knockdown protected cardiomyocytes from A/R-mediated apoptosis. Additional mechanistic studies revealed that circRNA_101237 served as a sponge for let-7a-5p, subsequently regulating insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)-dependent autophagy. IGF2BP3 downregulation decreased the levels of apoptosis and inhibited autophagy induced by A/R challenge in primary cardiomyocytes. These results identified circRNA_101237 as a novel circRNA that regulates cardiomyocyte death and autophagy, and demonstrated that the circRNA-101237/let-7a-5p/IGF2BP3 axis, which serves as a regulator of cardiomyocyte death, may be a potential therapeutic target for the management of cardiovascular diseases.

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Section: Introductionmentioning

confidence: 99%

Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let‑7a‑5p/IGF2BP3 in cardiomyocytes

et al. 2019

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“…Recently, abnormal circRNA expressions have been demonstrated in various cardiovascular diseases and cancers, which are related to vascular dysfunction. [6][7][8] Knockdown of cZNF609, which is highly enriched in endothelial cells, diminished retinal vessel loss and inhibited pathological angiogenesis in vivo. 9 CircRNA USP1 (circ-USP1, also known as hsa_circ_0000080 according to circBase), which is located at chr1p31, is derived from the back-splicing of exon 6-8 of ubiquitin-specific peptidase 1 (USP1) gene.…”

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confidence: 99%

Circular RNA USP1 regulates the permeability of blood‐tumour barrier via miR‐194‐5p/FLI1 axis

Gao

et al. 2019

J Cellular Molecular Medi

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Recent studies indicate circular RNAs are related to dysregulation of vascular endothelial cell function, yet the underlying mechanisms have remained elusive. Here, we characterized the functional role of circular RNA USP1 (circ‐USP1) in the regulation of the blood‐tumour barrier (BTB) permeability and the potential mechanisms. In the current study, the circ‐USP1 expressing level was up‐regulated in glioma cerebral microvascular endothelial cells (GECs) of the BTB model in vitro. Knockdown of circ‐USP1 disrupted the barrier integrity, increased its permeability as well as reduced tight junction‐related protein claudin‐5, occludin and ZO‐1 expressions in GECs. Bioinformatic prediction and luciferase assay indicated that circ‐USP1 bound to miR‐194‐5p and suppressed its activity. MiR‐194‐5p contributed to circ‐USP1 knockdown‐induced increase of BTB permeability via targeting and down‐regulating transcription factor FLI1. Furthermore, FLI1 regulated the expressions of claudin‐5, occludin and ZO‐1 in GECs through binding to their promoter regions. Single or combined treatment of circ‐USP1 and miR‐194‐5p effectively promoted anti‐tumour drug doxorubicin across BTB to induce apoptosis of glioma cells. Overall, this present study identified the crucial regulation of circ‐USP1 on BTB permeability via miR‐194‐5p/FLI1 axis‐mediated regulation of tight junction proteins, which might facilitate the development of therapeutics against human gliomas.

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“…Growing evidence has demonstrated that miRNAs play important roles in the regulation of development, differentiation, proliferation, and apoptosis [5, 6]. Notably, it has been reported that several miRNAs contribute to the development and progression of cardiac fibrosis [7-9]. For example, up-regulation of miR-21 [10], miR-34a and miR-93 [11] promoted the development of cardiac fibrosis, whereas overexpression of miR-133, and miR-590 [12], together with down-regulation of miR-23 [13], miR-29 [14], miR-101 [15] and miR-132 [16], suppressed the fibrotic responses of cardiac fibroblasts (CFs).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-323a-3p Promotes Pressure Overload-Induced Cardiac Fibrosis by Targeting TIMP3

Ling

Guo

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cardiac fibrosis is a major cause of diverse cardiovascular diseases. MicroRNAs have recently been proven a novel class of regulators of cardiac fibrosis. In this study, we sought to investigate the role of miR-323a-3p and its mechanisms in regulating cardiac fibrosis. Methods: The transverse aortic constriction (TAC) mice model was induced and neonatal cardiac fibroblasts (CFs) were cultured. MTT (3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay was used to detect the cell viability. Echocardiography was used to evaluate cardiac function. Masson’s Trichrome stain was used to evaluate the development of fibrosis. Luciferase activity assay was performed to confirm the miRNA’s binding site. Real-time PCR and Western blot were used to evaluate the level of mRNA and protein. Results: MiR-323a-3p was found up-regulated in myocardial tissues subjected to TAC and in CFs cultured with Angiotensin Ⅱ (Ang Ⅱ). Overexpression of miR-323a-3p significantly increased the mRNA levels of collagen Ⅰ, collagen Ⅲ, MMP2 and MMP9, while inhibition of miR-323a-3p prevented the proliferation, collagen production and the protein level of transforming growth factor (TGF-β) in rat neonatal CFs. Strikingly, injection of antagomiR-323a-3p elevated cardiac function and inhibited the expression of TGF-β in the TAC mice. TIMP3 was a direct target of miR-323a-3p, as the overexpression of miR-323a-3p decreased the protein and mRNA levels of TIMP3. In the CFs with pre-treatment of Ang Ⅱ, siRNA-TIMP abolished the effects of AMO-323a-3p on the inhibition of the proliferation of CFs, the down-regulation of collagen Ⅰ and collagen Ⅲ, and the expression of TGF-β. Conclusion: Our findings provide evidence that miR-323a-3p promotes cardiac fibrosis via miR-323a-3p-TIMP3-TGF-β pathway. miR-323a-3p may be a new marker for cardiac fibrosis progression and that inhibition of miR-323a-3p may be a promising therapeutic target for the treatment of cardiac fibrosis.

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Circular noncoding RNAs as potential therapies and circulating biomarkers for cardiovascular diseases

Cited by 87 publications

References 81 publications

Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let‑7a‑5p/IGF2BP3 in cardiomyocytes

Circular RNA_101237 mediates anoxia/reoxygenation injury by targeting let‑7a‑5p/IGF2BP3 in cardiomyocytes

Circular RNA USP1 regulates the permeability of blood‐tumour barrier via miR‐194‐5p/FLI1 axis

MicroRNA-323a-3p Promotes Pressure Overload-Induced Cardiac Fibrosis by Targeting TIMP3

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