LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells

Zhou, Yaqing; Zhang, Sheng; Ji, Wenfeng; Gan, Xiongkang; Liu, Hua; Hou, Can; Chen, Jiaxin; Wang, Yanjun; He, Shu; Zhou, Hongliang; Jia, En-Zhi

doi:10.3389/fcell.2021.656636

Cited by 11 publications

(8 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pipeline is highly efficient and expands the number of CAD-related vascular lncRNAs studied by previous efforts. 74,75 Through this work, we detected the expression of 4579 known and 13 655 de novo SMC transcripts, significantly increasing the number of SMC lncRNAs. Through experimental design, correlation analysis, construction of coexpression networks composed of pcGenes and lncRNAs, and genetic perturbation of individual lncRNAs in cultured HCASMC, we have been able to link numerous lncRNAs to CAD causal pcGenes and related pathways, considerably expanding the number of CAD-related lncRNAs.…”

Section: Discussionmentioning

confidence: 95%

“…24,[28][29][30][31][32][33][34][35] The function of several lncRNAs in atherosclerosis has been investigated in CAD-related cell types, providing evidence for the role of lncRNAs in CAD risk. Given that lncRNAs have been shown to be highly responsive to cellular stimulation, 74 we chose perturbations for HCASMC that specifically modulate CAD genome-wide association studies validated vascular cell disease pathways. A total of >18 billion strand-specific reads were obtained and examined with a discovery pipeline to identify both known and novel lncRNAs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Discovery of Transacting Long Noncoding RNAs That Regulate Smooth Muscle Cell Phenotype

Shi

Nguyen

Zhao

et al. 2023

Circulation Research

View full text Add to dashboard Cite

BACKGROUND: Smooth muscle cells (SMCs), the major cell type in atherosclerotic plaques, are vital in coronary artery diseases (CADs). Smooth muscle cell (SMC) phenotypic transition, which leads to the formation of various cell types in atherosclerotic plaques, is regulated by a network of genetic and epigenetic mechanisms and governs the risk of disease. The involvement of long noncoding RNAs (lncRNAs) has been increasingly identified in cardiovascular disease. However, SMC lncRNAs have not been comprehensively characterized, and their regulatory role in SMC state transition remains unknown. METHODS: A discovery pipeline was constructed and applied to deeply strand-specific RNA sequencing from perturbed human coronary artery SMC with different disease-related stimuli, to allow for the detection of novel lncRNAs. The functional relevance of a select few novel lncRNAs were verified in vitro. RESULTS: We identified 4579 known and 13 655 de novo lncRNAs in human coronary artery SMC. Consistent with previous long noncoding RNA studies, these lncRNAs overall have fewer exons, are shorter in length than protein-coding genes (pcGenes), and have relatively low expression level. Genomic location of these long noncoding RNA is disproportionately enriched near CAD-related TFs (transcription factors), genetic loci, and gene regulators of SMC identity, suggesting the importance of their function in disease. Two de novo lncRNAs, ZEB-interacting suppressor ( ZIPPOR ) and TNS1 -antisense ( TNS1-AS2 ), were identified by our screen. Combining transcriptional data and in silico modeling along with in vitro validation, we identified CAD gene ZEB2 as a target through which these lncRNAs exert their function in SMC phenotypic transition. CONCLUSIONS: Expression of a large and diverse set of lncRNAs in human coronary artery SMC are highly dynamic in response to CAD-related stimuli. The dynamic changes in expression of these lncRNAs correspond to alterations in transcriptional programs that are relevant to CAD, suggesting a critical role for lncRNAs in SMC phenotypic transition and human atherosclerotic disease.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Discovery of Transacting Long Noncoding RNAs That Regulate Smooth Muscle Cell Phenotype

Shi

Nguyen

Zhao

et al. 2023

Circulation Research

View full text Add to dashboard Cite

show abstract

“…Experimental protocols of RNA isolation, library construction, and sequencing were specifically described in our previous publication. 25 RNA was extracted according to standardized protocols. Briefly, RNA was separated with 200 μL of chloroform, precipitated with an equal volume of isopropanol, and washed with 1 mL of 75% ethanol.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…Experimental protocols of RNA isolation, library construction, and sequencing were specifically described in our previous publication . RNA was extracted according to standardized protocols.…”

Section: Methodsmentioning

confidence: 99%

Comprehensive Analysis of mRNA Expression Profiling and Identification of Potential Diagnostic Biomarkers in Coronary Artery Disease

Chen

Wang

et al. 2021

ACS Omega

Self Cite

View full text Add to dashboard Cite

The aim of this study is to investigate mRNA expression profiling by RNA sequencing (RNA-seq) in patients with coronary artery disease (CAD) and validate differentially expressed genes (DEGs) as novel biomarkers for CAD. Transcriptome-wide mRNA expression analysis of peripheral blood mononuclear cells was performed in five CAD patients and five controls. Functional enrichment analyses, protein− protein interaction network construction, and hub gene selection were further conducted. Relative expression levels of hub genes were validated by quantitative reverse transcription PCR in larger cohorts. Spearman correlation test and multiple linear regression analysis were applied to examine the relationship between confounding factors with severity of coronary artery atherosclerosis. Receiver operating characteristic (ROC) curve analysis was adopted to identify potentially diagnostic biomarkers for CAD. A total of 527 upregulated and 653 downregulated mRNAs were identified as DEGs in CAD patients. The relative expression levels of beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), F-box and leucine-rich repeat protein 4 (FBXL4), ubiquitin conjugating enzyme E2 D2 (UBE2D2), and ankyrin repeat and SOCS box containing 1 (ASB1) were significantly different between two groups (all p ≤ 0.05). The severity of coronary artery atherosclerosis was negatively associated with the BTRC gene relative expression level (r = −0.323, p < 0.001) and positively with UBE2D2 (r = 0.285, p < 0.001). ROC analysis of BTRC and UBE2D2 genes showed that the areas under the curve were 0.782 (95% CI: 0.720−0.845, p < 0.001) and 0.753 (95% CI: 0.681−0.824, p < 0.001), respectively. We described the characteristics of mRNA expression in the peripheral blood of CAD patients and controls by RNA-seq. Combined with Spearman correlation analysis and ROC analyses, BTRC and UBE2D2 genes had significantly diagnostic values, which may have potential to act as novel diagnostic biomarkers and therapeutic targets for CAD.

show abstract

“…All cells were placed in a humidi ed culture incubator with 5% CO2 at 37°C. In our previous study, the models of coronary atherosclerosis were successfully constructed with 50mg/L ox-LDL for 24 h (Zhou, et al, 2021).…”

Section: Sample Materialsmentioning

confidence: 99%

Identification and Characterization of N6-Methyladenosine LncRNAs in Human Coronary Artery Smooth Muscle Cells

Jiang

Gan

Zhou

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

N6-methyladenosine (m6A) is the most common internal RNA modification in mammalian cells. Lots of previous studies have shown that m6A is strongly linked to the occurrence and development of diseases. However, studies on the role of m6A modifications in atherosclerosis are limited and the possible mechanism needs to be elucidated. In this study, we used MeRIP-seq and RNA-seq to obtain a genome-wide profiling of m6A-modified lncRNAs in the model of coronary atherosclerosis. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify the reliability of the data. Functional enrichment analysis uncovered that the associated genes of lncRNAs with different m6A levels were mostly enriched in the regulation of many crucial cell biological processes, including cytoskeletal rearrangement, cell cycle, and Rap1 signaling pathway which can affect the proliferation and migration of vascular smooth muscle cells (VSMCs). In summary, our study provided an expressed profile of lncRNA m6A in Human Coronary Artery Smooth Muscle Cells(HCASMCs), and we can infer that the methylation state of lncRNA may be essential for their function and offer a new direction for the treatment ofcoronary artery disease(CAD).

show abstract

LncRNA Landscape of Coronary Atherosclerosis Reveals Differentially Expressed LncRNAs in Proliferation and Migration of Coronary Artery Smooth Muscle Cells

Cited by 11 publications

References 28 publications

Discovery of Transacting Long Noncoding RNAs That Regulate Smooth Muscle Cell Phenotype

Discovery of Transacting Long Noncoding RNAs That Regulate Smooth Muscle Cell Phenotype

Comprehensive Analysis of mRNA Expression Profiling and Identification of Potential Diagnostic Biomarkers in Coronary Artery Disease

Identification and Characterization of N6-Methyladenosine LncRNAs in Human Coronary Artery Smooth Muscle Cells

Contact Info

Product

Resources

About