CDR1as/miR‑7/CKAP4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells

Zhao, Feng; Chen, Tongyun; Jiang, Nan

doi:10.3892/etm.2020.8622

Cited by 26 publications

(22 citation statements)

References 31 publications

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“…Studies have revealed that circRNAs principally bind to miRNAs to act as RNA sponges and increase downstream gene expression by inhibiting miRNA activities, thus contributing to disease progression ( Song et al, 2020 ; Wang et al, 2016 ; Zhao, Chen & Jiang, 2020 ). Similarly, for circHIPK3, the most classical mechanism for its functional effect is to act as a sponge for miRNAs, blocking the binding of miRNAs with downstream target genes and regulating the expression of target genes.…”

Section: Discussionmentioning

confidence: 99%

CircHIPK3 regulates cardiac fibroblast proliferation, migration and phenotypic switching through the miR-152-3p/TGF-β2 axis under hypoxia

Liu

Wang

Qiu

et al. 2020

PeerJ

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Background The occurrence of pathological cardiac fibrosis is attributed to tissue hypoxia. Circular RNAs play significant regulatory roles in multiple cardiovascular diseases and are involved in the regulation of physiological and pathophysiological processes. CircHIPK3 has been identified as the one of the most crucial regulators in cardiac fibrosis. However, the mechanisms by which circHIPK3 regulates cardiac fibrosis under hypoxia remain unclear. Our study aimed to determine circHIPK3 expression in cardiac fibroblasts (CFs) and investigate the functions of circHIPK3 in hypoxia environment. Methods The expression level of circHIPK3 in CFs under hypoxia (1% O2) was analyzed by qRT-PCR. The role of circHIPK3 on the proliferation and migration of CFs were determined by EdU, cell wound scratch assay and cell cycle. The expression of proteins associated with phenotypic transformation in CFs in vitro was examined by immunofluorescence assay and western blot. Bioinformatics analysis, dual luciferase activity assay and RNA fluorescent in situ hybridization assay revealed that miR-152-3p was identified as a target of circHIPK3 and that TGF-β2 was targeted by miR-152-3p. Results CircHIPK3 expression was significantly upregulated in CFs in a hypoxic environment. In vitro, overexpressing circHIPK3 obviously promoted CF proliferation, migration and phenotypic changes under hypoxia, but those processes were suppressed by circHIPK3 silencing. CircHIPK3 acted as an endogenous miR-152-3p sponge and miR-152-3p aggravated circHIPK3 silencing induced inhibition of CF proliferation, migration, phenotypic transformation and TGF-β2 expression in vitro. In summary, circHIPK3 plays a pivotal role in the development of cardiac fibrosis by targeting the miR-152-3p/TGF-β2 axis. Conclusions These findings demonstrated that circHIPK3 acted as a miR-152-3p sponge to regulate CF proliferation, migration and phenotypic transformation through TGF-β2, revealing that modulation of circHIPK3 expression may represent a potential target to promote the transition of hypoxia-induced CFs to myofibroblasts.

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Section: Discussionmentioning

confidence: 99%

CircHIPK3 regulates cardiac fibroblast proliferation, migration and phenotypic switching through the miR-152-3p/TGF-β2 axis under hypoxia

Liu

Wang

Qiu

et al. 2020

PeerJ

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“…circ_0020397 plays an important role in the phenotypic modulation of intracranial aneurysms by promoting VSMC viability via the miR-502-5p/GREM1 axis ( 56 ). Additionally, CDR1as serves as a sponge for miR-7, which increases the expression of CKAP4 to facilitate the proliferation and suppress the apoptosis of VSMCs, leading to VSMC remodeling and progression of abdominal aortic aneurysm (AAA) ( 57 ). circCBFB facilitates VSMC proliferation and inhibits VSMC apoptosis via the circCBFB/miR-28-5p/GRIA4/LYPD3 axis ( 58 ).…”

Section: Circrna As Cerna In Cvdsmentioning

confidence: 99%

Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

Xue

Liu

Xiong

2021

Front. Cardiovasc. Med.

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Circular RNAs (circRNAs) represent a novel class of widespread and diverse endogenous RNA molecules. This unusual class of RNA species is generated by a back-splicing event of exons or introns, resulting in a covalently closed circRNA molecule. Accumulating evidence indicates that circRNA plays an important role in the biological functions of a network of competing endogenous RNA (ceRNA). CircRNAs can competitively bind to miRNAs and abolish the suppressive effect of miRNAs on target RNAs, thus regulating gene expression at the posttranscriptional level. The role of circRNAs as ceRNAs in the pathogenesis of cardiovascular and cerebrovascular diseases (CVDs) has been recently reported and highlighted. Understanding the underlying molecular mechanism could aid the discovery of therapeutic targets or strategies against CVDs. Here, we review the progress in studying the role of circRNAs as ceRNAs in CVDs, with emphasis on the molecular mechanism, and discuss future directions and possible clinical implications.

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“…There are over 70 miR-7 binding sites in the cerebellar degeneration-related protein 1 antisense RNA (CDR1as), and these sites regulate the effect of CDR1as on the target gene expression [ 93 ]. According to recent research, the expression levels of CDR1as and CKAP4 (the estimated miR-7 target) are lower in AAA cases than those in normal controls [ 94 ]. Zhao et al suggested that the CDR1as/miR-7/CKAP4 axis plays a role in VSMCs of AAA cases and that CDR1as upregulation may curb the expression of miR-7.…”

Section: Verified Circrnas In Aaasmentioning

confidence: 99%

Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

Han

Zhang

Bian

et al. 2021

Oxidative Medicine and Cellular Longevity

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Abdominal aortic aneurysms (AAAs) have posed a great threat to human life, and the necessity of its monitoring and treatment is decided by symptomatology and/or the aneurysm size. Accumulating evidence suggests that circular RNAs (circRNAs) contribute a part to the pathogenesis of AAAs. circRNAs are novel single-stranded RNAs with a closed loop structure and high stability, having become the candidate biomarkers for numerous kinds of human disorders. Besides, circRNAs act as molecular “sponge” in organisms, capable of regulating the transcription level. Here, we characterize that the molecular mechanisms underlying the role of circRNAs in AAA development were further elucidated. In the present work, studies on the biosynthesis, bibliometrics, and mechanisms of action of circRNAs were aims comprehensively reviewed, the role of circRNAs in the AAA pathogenic mechanism was illustrated, and their potential in diagnosing AAAs was examined. Moreover, the current evidence about the effects of circRNAs on AAA development through modulating endothelial cells (ECs), macrophages, and vascular smooth muscle cells (VSMCs) was summarized. Through thorough investigation, the molecular mechanisms underlying the role of circRNAs in AAA development were further elucidated. The results demonstrated that circRNAs had the application potential in the diagnosis and prevention of AAAs in clinical practice. The study of circRNA regulatory pathways would be of great assistance to the etiologic research of AAAs.

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CDR1as/miR‑7/CKAP4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells

Cited by 26 publications

References 31 publications

CircHIPK3 regulates cardiac fibroblast proliferation, migration and phenotypic switching through the miR-152-3p/TGF-β2 axis under hypoxia

CircHIPK3 regulates cardiac fibroblast proliferation, migration and phenotypic switching through the miR-152-3p/TGF-β2 axis under hypoxia

Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

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