The microRNA <i>miR‐134‐5p</i> induces calcium deposition by inhibiting histone deacetylase 5 in vascular smooth muscle cells

Choe, Nakwon; Shin, Sera; Joung, Hosouk; Ryu, Jin-Sook; Kim, Young‐Kook; Ahn, Youngkeun; Kook, Hyun; Kwon, Duk-Hwa

doi:10.1111/jcmm.15670

Cited by 8 publications

(8 citation statements)

References 57 publications

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“…miR-25 protects glucocorticoid-induced apoptotic process in VSMCs thereby reducing vascular calcification ( Zhang et al, 2019 ). miR-134-5p exacerbates vascular calcification by regulating the expression of histone deacetylase 5 in high phosphate conditions ( Choe et al, 2020b ). CircSmoc1-2 attenuates vascular calcification by regulating the miR-874-3p/Adam19 axis ( Ryu et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential biomarkers of vascular calcification using bioinformatics analysis and validation in vivo

Chen

et al. 2022

PeerJ

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Background Vascular calcification (VC) is the most widespread pathological change in diseases of the vascular system. However, we know poorly about the molecular mechanisms and effective therapeutic approaches of VC. Methods The VC dataset, GSE146638, was downloaded from the Gene Expression Omnibus (GEO) database. Using the edgeR package to screen Differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to find pathways affecting VC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the DEGs. Meanwhile, using the String database and Cytoscape software to construct protein-protein interaction (PPI) networks and identify hub genes with the highest module scores. Correlation analysis was performed for hub genes. Receiver operating characteristic (ROC) curves, expression level analysis, GSEA, and subcellular localization were performed for each hub gene. Expression of hub genes in normal and calcified vascular tissues was verified by quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry (IHC) experiments. The hub gene-related miRNA-mRNA and TF-mRNA networks were constructed and functionally enriched for analysis. Finally, the DGIdb database was utilized to search for alternative drugs targeting VC hub genes. Results By comparing the genes with normal vessels, there were 64 DEGs in mildly calcified vessels and 650 DEGs in severely calcified vessels. Spp1, Sost, Col1a1, Fn1, and Ibsp were central in the progression of the entire VC by the MCODE plug-in. These hub genes are primarily enriched in ossification, extracellular matrix, and ECM-receptor interactions. Expression level results showed that Spp1, Sost, Ibsp, and Fn1 were significantly highly expressed in VC, and Col1a1 was incredibly low. RT-qPCR and IHC validation results were consistent with bioinformatic analysis. We found multiple pathways of hub genes acting in VC and identified 16 targeting drugs. Conclusions This study perfected the molecular regulatory mechanism of VC. Our results indicated that Spp1, Sost, Col1a1, Fn1, and Ibsp could be potential novel biomarkers for VC and promising therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Identification of potential biomarkers of vascular calcification using bioinformatics analysis and validation in vivo

Chen

et al. 2022

PeerJ

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“…20 ncRNAs can function as both positive and negative regulators of VC. 21 We recently reported that miR-134-5p induces VC by suppressing histone deacetylase 5, 22 and miR-27a-3p targets ATF3 to inhibit VC in vascular smooth muscle cells (VSMCs). 23 In addition, we found that the lncRNA Lrrc75a-as1 works as a negative mediator of VC and inhibits osteoblast-related factors.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circSmoc1-2 regulates vascular calcification by acting as a miR-874-3p sponge in vascular smooth muscle cells

Ryu

Choe

Kwon

et al. 2022

Molecular Therapy - Nucleic Acids

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Vascular calcification (VC), or calcium deposition inside the blood vessels, is common in patients with atherosclerosis, cardiovascular disease, and chronic kidney disease. Although several treatments are available to reduce calcification, the incidence of VC continues to rise. Recently, there have been several reports describing the regulation of circular RNAs (circRNAs) in various diseases. However, the role of circRNAs in VC has not yet been fully explored. Here, we investigated the function of circSmoc1-2, one of the circRNAs generated from the Smoc1 gene, which is downregulated in response to VC. CircSmoc1-2 is localized primarily to the cytoplasm and is resistant to exonuclease digestion. Inhibition of circSmoc1-2 worsens VC, while overexpression of circSmoc1-2 reduces VC, suggesting that circSmoc1-2 can prevent calcification. We went on to investigate the mechanism of circSmoc1-2 as a microRNA sponge and noted that miR-874-3p, the predicted target of circSmoc1-2, promotes VC, while overexpression of circS-moc1-2 reduces VC by suppressing miR-874-3p. Additionally, we identified the potential mRNA target of miR-874-3p as Adam19. In conclusion, we revealed that the circSmoc1-2/ miR-874-3p/Adam19 axis regulates VC, suggesting that circS-moc1-2 may be a novel therapeutic target in the treatment of VC.

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“…VSMCs were cultured in Dulbecco's modi ed Eagle's medium (DMEM) containing 10% FBS, and 1% penicillin-streptomycin at 37°C with 5% CO 2 . To induce calci cation, VSMCs at passage 3 were treated with 10 mM β-glycerophosphate (Sigma, St Louis, MO, USA) for total six days as previously reported (6). After washing with PBS for twice, the quanti cation of calcium deposition was evaluated by using Alizarin Red staining.…”

Section: Cell Isolation Culture and Construction Of Calci Cation Modelmentioning

confidence: 99%

“…A large number of miRNAs have been identi ed to participate in the metabolic process of calcium deposition, and potentially acted as e cient predictors for vascular calci cation. For example, miR-134-5p induces calcium deposition by inhibiting the expression of histone deacetylase 5 in VSMCs (6). MiR-135a has been demonstrated to suppress the calci cation in senescent VSMCs by modulating KLF4/STAT3 signaling pathway (7).…”

Section: Introductionmentioning

confidence: 99%

Exosomal miR-151-3p Induces Calcium Deposition in Vascular Smooth Muscle Cells by Inhibiting Atg5

Chen

Zhang

Jin-yin

et al. 2021

Preprint

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Background: Calcium deposition in vascular smooth muscle cells (VSMCs) can lead to the rigidity of the vasculature and an increase of risk in cardiac events. This study aimed to explore the role of exosomal microRNA-151-3p (miR-151-3p) in the regulation of VSMC calcification. Methods: A cellular calcification model was established using the mouse primary aortic VSMCs by β-glycerophosphate treatment. The calcium deposition was evaluated by Alizarin Red staining. The expression of miR-151-3p in exosomes was evaluated by qRT-PCR. The relationship between miR-151-3p and Atg5 was determined by bioinformatics analysis and dual-luciferase gene reporter assay. The exosome derived from mouse VSMCs transfected with miR-151-3p mimics/inhibitor were isolated and used to stimulate VSMCs. The expression of Atg5, α-SMA, OPN, Runx2 and BMP2 was evaluated by western blot. An animal model was established to investigate the role of miR-151-3p in exosomes.Results: MiR-151-3p was significantly upregulated in the exosomes of VSMCs treated with β-glycerophosphate. Exosomes derived from calcific VSMCs increased the calcium deposition of general VSMCs without any treatment. Exosomes derived from miR-151-3p mimics transfected VSMCs increased the expression of Runx2 and BMP2, while reduced the expression of α-SMA and OPN in general VSMCs. and exosomes derived from miR-151-3p inhibitor transfected VSMCs reversed these effects in vitro. Meanwhile, miR-151-3p served as a ceRNA of Atg5 by directly binding to the 3'UTR of Atg5. Moreover, the expression of α-SMA, OPN, Runx2 and BMP2 in vivo was consistent with the results in VSMCs in vitro.Conclusion: Our study revealed that miR-151-3p in VSMCs-derived exosomes might induce calcium deposition through regulating Atg5 expression, suggesting that miR-151-3p might be a potential biomarker for vascular calcification.

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The microRNA miR‐134‐5p induces calcium deposition by inhibiting histone deacetylase 5 in vascular smooth muscle cells

Cited by 8 publications

References 57 publications

Identification of potential biomarkers of vascular calcification using bioinformatics analysis and validation in vivo

Identification of potential biomarkers of vascular calcification using bioinformatics analysis and validation in vivo

Circular RNA circSmoc1-2 regulates vascular calcification by acting as a miR-874-3p sponge in vascular smooth muscle cells

Exosomal miR-151-3p Induces Calcium Deposition in Vascular Smooth Muscle Cells by Inhibiting Atg5

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