CircMTO1 inhibits ox-LDL-stimulated vascular smooth muscle cell proliferation and migration via regulating the miR-182-5p/RASA1 axis

Ji, Ningfei; Wang, Yu; Gong, Xinyan; Ni, Shimao; Zhang, Hui

doi:10.1186/s10020-021-00330-2

Cited by 12 publications

(6 citation statements)

References 43 publications

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“… 3 It is widely reported that circRNA plays an important role in cell and tissue proliferation. 4 , 5 For example, circGCN1L1 promotes cell proliferation and apoptosis by targeting miR-330-3p and TNF-α. 6 CircRNAs play important roles in CRSwNP occurrence.…”

Section: Introductionmentioning

confidence: 99%

Identification of a circRNA/miRNA/mRNA ceRNA Network as a Cell Cycle-Related Regulator for Chronic Sinusitis with Nasal Polyps

Sun¹,

Liu²,

Xu³

et al. 2022

JIR

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Purpose To explore the mechanisms by which circRNA/miRNA/mRNA competitive endogenous RNAs (ceRNA) networks regulate CRSwNP. Methods The expression profiles of circRNAs, miRNAs, and mRNAs from patients with CRSwNP and control subjects were acquired from the Gene Expression Omnibus database. The circRNA/miRNA/mRNA ceRNA network was constructed based on the predicted circRNA–miRNA interactions and miRNA–mRNA interactions. Hub-mRNAs were screened by protein–protein interaction network analysis and Cytoscape molecular complex detection. The expression of factors in tissue and in hsa_circ_0031594 siRNA transfection cells was verified by RT-qPCR and the association between them was revealed by Spearman correlation analysis. Receiver operating characteristic curve analysis was performed with the pROC R package. Results The differential expression of 5423 circRNAs, 415 miRNAs, and 3673 mRNAs was identified in CRSwNP subjects compared to control subjects. Among these, 9 circRNAs, 39 miRNAs, and 78 mRNAs were screened to construct a ceRNA network. Ultimately, a subnetwork including circRNA hsa_circ_0031594, hsa-miR-1260b, hsa-miR-6507-5p, NCAPG2, RACGAP1, CHEK1 and PRC1 was screened out. RT-qPCR validated that the expression of hsa_circ_0031594, NCAPG2, PRC1 was significantly increased, and hsa-miR-1260b and hsa-miR-6507-5p were expressed significantly less in patients with CRSwNP than in control subjects. In addition, the AUCs of hsa_circ_0031594, hsa-miR-1260b, hsa-miR-6507-5p, NCAPG2, and PRC1 to discriminate CRSwNP patients were 0.995, 0.842, 0.862, 0.765, and 0.816. Spearman correlation showed that the expression of hsa_circ_0031594 was negatively correlated with hsa-miR-1260b and hsa-miR-6507-5p, and positively correlated with NCAPG2 and PRC1. In human nasal epithelial cell (HNEpC) line, knocking down hsa_circ_0031594 could increase the expression of hsa-miR-1260b and hsa-miR-6507-5p, and reduce the expression of NCAPG2 and PRC1. Conclusion CeRNA networks including hsa_circ_0031594, hsa-miR-1260b, and NCAPG2, and hsa_circ_0031594, hsa-miR-6507-5p, and PRC1 may be key regulators for CRSwNP occurrence, and may be potential targets for the pathogenesis and treatment development of CRSwNP.

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Section: Introductionmentioning

confidence: 99%

Identification of a circRNA/miRNA/mRNA ceRNA Network as a Cell Cycle-Related Regulator for Chronic Sinusitis with Nasal Polyps

Sun¹,

Liu²,

Xu³

et al. 2022

JIR

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“…However, lower levels of circMTO1 in the serum of humans with atherosclerosis coincided with augmentation of miR-182-5p, increased proliferation, and reduced apoptosis in an in vitro analysis of ox-LDL-stimulated VSMCs. Overexpression of circMTO1 led to less inhibition of miR-182-5p and subsequently greater activation of the RASA1 gene, reduced proliferation, and increased apoptosis of VSMCs [ 57 ]. Similarly, while lower levels of circ_0065149 were observed in a model of ox-LDL human umbilical vein ECs in vitro, overexpression was associated with miR-330-5p sponging and associated effects of increased cell viability, proliferation, and migration, but reduced apoptosis and inflammation [ 62 ].…”

Section: Resultsmentioning

confidence: 99%

“…Sponging the same miRNA by different circRNAs also had contradictory effects on cell proliferation, apoptosis, and inflammation. For example, miR-182-5p was demonstrated to be affected downstream of four different circRNA molecules: circ_USP36, circMTO1, hsa_circ_0004831, and Circ_0050486 [ 42 , 57 , 77 , 142 ]. While sponging of miR-182-5p by circ_USP36 led to increased activity of the KLF5 gene, which induced VSMC proliferation and metastasis, inhibition of miR-182-5p via overexpression of circMTO1 and subsequent RASA1 gene activation had the opposite effects of decreased VSMC proliferation and decreased apoptosis ( Table S1 ).…”

Section: Discussionmentioning

confidence: 99%

“…A search of the online PubMed database for publications from 2016 to 2022 was conducted using the following keywords: circular RNA, atherosclerosis, coronary artery disease, oxidized low-density lipoprotein, vascular smooth muscle cells, and endothelial cells. A total of 140 original research articles were included, and their findings are summarized in Table S1 [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , …”

Section: Methodsmentioning

confidence: 99%

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Circular RNA as Therapeutic Targets in Atherosclerosis: Are We Running in Circles?

Triska

Mathew

Zhao

et al. 2023

JCM

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Much attention has been paid lately to harnessing the diagnostic and therapeutic potential of non-coding circular ribonucleic acids (circRNAs) and micro-RNAs (miRNAs) for the prevention and treatment of cardiovascular diseases. The genetic environment that contributes to atherosclerosis pathophysiology is immensely complex. Any potential therapeutic application of circRNAs must be assessed for risks, benefits, and off-target effects in both the short and long term. A search of the online PubMed database for publications related to circRNA and atherosclerosis from 2016 to 2022 was conducted. These studies were reviewed for their design, including methods for developing atherosclerosis and the effects of the corresponding atherosclerotic environment on circRNA expression. Investigated mechanisms were recorded, including associated miRNA, genes, and ultimate effects on cell mechanics, and inflammatory markers. The most investigated circRNAs were then further analyzed for redundant, disparate, and/or contradictory findings. Many disparate, opposing, and contradictory effects were observed across experiments. These include levels of the expression of a particular circRNA in atherosclerotic environments, attempted ascertainment of the in toto effects of circRNA or miRNA silencing on atherosclerosis progression, and off-target, cell-specific, and disease-specific effects. The high potential for detrimental and unpredictable off-target effects downstream of circRNA manipulation will likely render the practice of therapeutic targeting of circRNA or miRNA molecules not only complicated but perilous.

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“…Moreover, circMTO1 represses the proliferative and migrative abilities of VSMCs stimulated by Ox-LDL via the miR-182-5p/RASA1 axis. 16 miR-663 has been elucidated to manipulate the phenotype change of human VSMCs and vascular neointimal formation and play an active role in VSMCs proliferation. 17 In addition, miR-663 plays an indispensable role in endothelial dysfunction, AS, and inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Effect of miR-663 on atherosclerosis by regulating the proliferation of vascular smooth muscle cells in lipid plaques

Deng

2022

Vascular

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Objectives Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. microRNAs (miRNAs) are widely distributed in the human body and closely related to the pathological progress of AS. This study probed into the function of miR-663 in AS. Methods The atherosclerotic plaques, cholesterol (CHOL), low-density lipoprotein (LDL), inflammatory factors, and miR-663 expression in ApoE−/− mice on high-fat diet were evaluated. The overexpressing miR-663 adenovirus was injected into ApoE−/− mice, followed by measurement of type III collagen (Col III), matrix metalloproteinase (MMP)-2, α-SMA, osteopontin, and CD31. miR-663 mimic or inhibitor was introduced into vascular smooth muscle cells (VSMCs) stimulated by oxidized LDL (Ox-LDL), and cell proliferation and IL-6 and IL-18 secretion were evaluated. The binding relationship between miR-663 and HMGA2 was verified, followed by the determination of HMGA2 role in VSMC proliferation. Results Atherosclerotic plaques appeared in ApoE−/− mice on high-fat diet, with increased CHOL, LDL, osteopontin, MMP-2 and Col III and decreased miR-663, α-SMA and CD31. miR-663 overexpression downregulated osteopontin, MMP-2 and Col III and upregulated α-SMA and CD31 in ApoE−/− mice on high-fat diet. With Ox-LDL concentration increase, VSMC proliferation was promoted and miR-663 was downregulated. miR-663 overexpression inhibited proliferation of Ox-LDL-stimulated VSMCs and reduced levels of inflammatory factor levels, whereas silencing miR-663 did the opposite. miR-663 targeted HMGA2. HMGA2 overexpression partially reversed the inhibitory effect of miR-663 overexpression on VSMC proliferation. Conclusion miR-663 targeted HMGA2 to inhibit VSMC proliferation and AS development, which may offer insights into AS treatment.

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CircMTO1 inhibits ox-LDL-stimulated vascular smooth muscle cell proliferation and migration via regulating the miR-182-5p/RASA1 axis

Cited by 12 publications

References 43 publications

Identification of a circRNA/miRNA/mRNA ceRNA Network as a Cell Cycle-Related Regulator for Chronic Sinusitis with Nasal Polyps

Identification of a circRNA/miRNA/mRNA ceRNA Network as a Cell Cycle-Related Regulator for Chronic Sinusitis with Nasal Polyps

Circular RNA as Therapeutic Targets in Atherosclerosis: Are We Running in Circles?

Effect of miR-663 on atherosclerosis by regulating the proliferation of vascular smooth muscle cells in lipid plaques

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