Expression pattern of miR-21, miR-25 and PTEN in peripheral blood mononuclear cells of patients with significant or insignificant coronary stenosis

Nariman‐Saleh‐Fam, Ziba; Vahed, Sepideh Zununi; Aghaee‐Bakhtiari, Seyed Hamid; Daraei, Abdolreza; Saadatian, Zahra; Kafil, Hossein Samadi; Yousefi, Bahman; Eyvazi, Shirin; Khaheshi, Isa; Parsa, Saeed; Moravej, Ali; Mousavi, Negar; Bastami, Milad; Mansoori, Yaser

doi:10.1016/j.gene.2019.02.074

Cited by 35 publications

(20 citation statements)

References 51 publications

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“…However, to the best of our knowledge, the association between geniposide and miR-21/PTEN has not yet been reported. The present study found that ox-LdL treatment significantly resulted in inhibition of the miR-21/PTEN pathway, which is consistent with previous studies (24,43). Notably, these effects were reversed by geniposide pretreatment, indicating geniposide induced the activation of the miR-21/PTEN pathway under ox-LdL condition.…”

Section: Discussionsupporting

confidence: 93%

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

et al. 2020

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Oxidized low-density lipoprotein (ox-LdL)-induced vascular endothelial damage, oxidative stress and inflammation play a vital role in the pathophysiology of atherosclerosis. Geniposide is the primary active ingredient from Gardenia jasminoides Ellis associated with anti-oxidative properties and cardioprotective action. However, the therapeutic mechanism of geniposide in atherosclerosis remains unclear. Hence, the present study aimed to elucidate the underlying mechanisms of geniposide in oxidative stress and inflammatory response during ox-LdL injury in human umbilical vein endothelial cells (HUVEcs), focusing particularly on the microRNA (miR)-21/PTEN pathway. The results demonstrated that geniposide pretreatment significantly increased cell viability, decreased lactate dehydrogenase release, increased miR-21 level and decreased PTEN expression under ox-LdL condition. Subsequently, transfection with miR-21 mimic enhanced the protection of geniposide on ox-LdL-induced cytotoxicity and apoptosis (mediated by the upregulation of apoptotic rate and caspase-3 activity), whereas miR-21 inhibitor reversed these effects of geniposide. In addition, geniposide resulted in an anti-oxidant effect as evidenced by the decrease in reactive oxygen species generation, malondialdehyde content and NAdPH oxidase 2 expression, and the increase in superoxide dismutase, glutathione peroxidase and catalase activities in ox-LdL-treated HUVEcs, which were exacerbated by miR-21 mimic and reversed by miR-21 inhibitor. Furthermore, geniposide mitigated the ox-LdL-induced inflammatory response, demonstrated by a downregulation of pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) levels and an upregulation of anti-inflammatory cytokine (IL-10) level. However, miR-21 mimic enhanced, whereas miR-21 inhibitor attenuated, these effects of geniposide. In conclusion, the present results indicated that geniposide protects HUVEcs from ox-LdL injury by inhibiting oxidative stress and inflammation, and that these effects are partly due to the enhancement of the miR-21/PTEN pathway.

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Section: Discussionsupporting

confidence: 93%

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

et al. 2020

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“…In view of the small sample size of datasets obtained from GEO database and accumulative deviation from bioinformatics analysis, we performed laboratorial verification with relatively larger sample size [35]. Previous reports suggested PTEN was up-regulated in peripheral blood mononuclear cells of CAD patients, which was consistent with our founding in PBLs and confirmed the reliability of our research [36]. In addition to the involvement of microRNAs in the regulation of PTEN, we conjectured DNA methylation might also participated in the regulation network.…”

Section: Discussionsupporting

confidence: 87%

Identification of potential biomarkers for CAD using integration with expression and methylation data and validation by case-control study

Zhang

Xiang

et al. 2020

Preprint

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Background: DNA methylation plays an essential role in the pathogenesis of coronary artery disease (CAD) through regulating mRNA expressions. This study aimed to identify hub genes as biomarkers functioning in CAD and regulated by DNA methylation. Methods: Gene expression and methylation datasets of peripheral blood leukocytes (PBLs) of CAD were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified based on differentially methylated CpG sites (DMCs) in intragenic regions. The overlapped genes in DEGs and DMGs were filtered and defined as differentially expressed-methylated genes (DEMGs). Multiple computational approaches were performed to analyze the regulatory networks of DEMGs and recognize hub genes, subsequently. Finally, top hub genes were verified in a case-control study based on their differential expression levels between CAD cases and controls. Results: Totally 535 DEMGs were identified and partitioned into 4 subgroups. TSS200 and 5’UTR were confirmed as high enrichment areas of DMCs. DEMGs mainly enriched in processes of histone H3-K27 methylation, regulation of posttranscription and DNA-directed RNA polymerase activity. Pathway enrichment showed DEMGs participated in VEGF signaling pathway, adipocytokine signaling pathway and PI3K-Akt signaling pathway. Besides, hub genes FN1 (fibronectin 1), PTEN (phosphatase and tensin homolog), POLR3A (RNA polymerase III subunit A) were experimentally proved discordantly expressed in CAD patients when compared with controls. Conclusions: In conclusion, our study demonstrated the probable functional genes of PBLs in CAD, in which FN1, PTEN and POLR3A were confirmed. The underlying mechanism that differential expression-methylation of FN1, PTEN and POLR3A in CAD need further study.

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“…Moreover, microRNA-21 expressions in naive CD4+ T cells were amazingly elevated in (65-85 years) older healthy subjects compared with (20-35 years) younger subjects, with higher variance in the geriatric subjects, suggesting miR-21 remarkably controlled immune response and aging [14]. Very recently, it was reported that the expression pattern of circulating microRNA-21 was greatly associated with significant or insignificant coronary stenosis patients [15]. However, the clinical significance of plasma microRNA-21 for coronary artery disease patients and linked with aging is not fully explored.…”

Section: Introductionmentioning

confidence: 97%

Diagnostic Role of Plasma MicroRNA-21 in Stable and Unstable Angina Patients and Association with Aging

Sheikh

2020

Cardiology Research and Practice

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The present study explored the clinical value of plasma microRNA-21 as a novel biomarker for early prediction of stable and unstable angina patients and its relationship with aging. A total of 255 participants, 123 patients with chronic stable angina, 82 patients with unstable angina, and 50 healthy subjects, were included in our study. Stable coronary and unstable coronary patients were confirmed following AHA/ACC clinical protocols. Total RNA was extracted from plasma by using miRNA-based TRIzol reagent. Plasma miR-21 expression levels were determined by real-time polymerase chain reaction. To evaluate the diagnosis accuracy, the receiver operating characteristic (ROC) curves were used. Plasma microRNA-21 concentration levels were significantly elevated in stable and unstable angina patients as compared with control subjects P<0.001. The area under the ROC curves of circulating microRNA-21 was accurately distinguished in stable angina patients (AUC 0.921) and unstable angina patients (AUC 0.944) from healthy subjects. MicroRNA-21 expression gradually elevated with increasing aging in all the populations. Moreover, the current study also demonstrated that the expression of plasma miR-21 levels was significantly associated with different age groups within healthy subjects and stable and unstable angina patients P<0.001. This research finding suggested that plasma microRNA-21 may be considered as a suitable new biomarker for early detection of stable and unstable angina patients, and it has a strong correlation with aging.

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Expression pattern of miR-21, miR-25 and PTEN in peripheral blood mononuclear cells of patients with significant or insignificant coronary stenosis

Cited by 35 publications

References 51 publications

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

miR‑21/PTEN pathway mediates the cardioprotection of geniposide against oxidized low‑density�lipoprotein‑induced endothelial injury via suppressing oxidative stress and inflammatory response

Identification of potential biomarkers for CAD using integration with expression and methylation data and validation by case-control study

Diagnostic Role of Plasma MicroRNA-21 in Stable and Unstable Angina Patients and Association with Aging

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