Serum Exosomal microRNA-27-3p Aggravates Cerebral Injury and Inflammation in Patients with Acute Cerebral Infarction by Targeting PPARγ

Ye, Zhinan; Hu, Jingchun; Xu, Hao; Sun, Bin; Zhang, Yaping; Zhang, Jianli

doi:10.1007/s10753-020-01399-3

Cited by 30 publications

(22 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 Emerging studies have unveiled the differential expression of miRNAs in the serum of ACI patients. 8,14 This study demonstrated the downregulation of miR-124 in the serum of ACI patients, with favorable diagnostic and prognostic value. Dysregulated miRNA expression is implicated in the pathogenesis of ACI.…”

Section: Discussionmentioning

confidence: 64%

“…6 Accumulating studies have unveiled the aberrant expression of miRNAs in the brain tissues and peripheral blood of ACI patients, implying that miRNAs are implicated in the pathogenesis, diagnosis, and prognosis of ACI. 2,7,8 miR-124 is identified as one of the most abundant miRNAs in the human brain that modulates variant biological functions of the central nervous system (CNS), and dysregulated miR-124 is tightly associated with stroke. 9 The elevated miR-124 expression has the property to reduce the infarct size and facilitate the recovery of neurological functions post-ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

miR-124 Is Downregulated in Serum of Acute Cerebral Infarct Patients and Shows Diagnostic and Prognostic Value

Zhou

2021

Clin Appl Thromb Hemost

View full text Add to dashboard Cite

Acute cerebral infarct (ACI) is a severe subtype of ischemic stroke. microRNAs (miRNAs) are implicated in the pathogenesis of ACI. This study investigated the expression pattern and clinical implication of miR-124 in ACI patients. Serum samples were collected from 108 healthy people and 108 ACI patients at 24 h, 48 h, and 72 h. Serum miR-124 expression was tested using qRT-PCR. The levels of interleukin (IL)-6, IL-8, and C-reactive protein (CRP) were detected using ELISA kits. The correlations between miR-124 expression and infarct classification, infarct size, risk factors, and inflammatory factors were analyzed. The diagnostic efficacy of miR-124 in ACI was analyzed by the ROC curve. ACI patients were assigned to the miR-124 high/low expression group and the incidence of poor prognosis was compared between the two groups. miR-124 expression was poorly expressed in the serum of ACI patients. The area under the ROC curve of miR-124 in the diagnosis of ACI was 0.9527, the specificity was 91.67%, and the sensitivity was 93.52%. miR-124 expression in ACI patients was not affected by infarct classification, infarct size, low-density lipoprotein level, and homocysteine level. miR-124 expression was negatively correlated with IL-6, IL-8, and CRP in ACI patients. Low expression of miR-124 was positively correlated with the poor prognosis of ACI. miR-124 was poorly expressed in the serum of ACI patients and served as a biomarker for the diagnosis and prognosis. This study shall confer a promising novel target for the diagnosis and treatment of ACI.

show abstract

Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

miR-124 Is Downregulated in Serum of Acute Cerebral Infarct Patients and Shows Diagnostic and Prognostic Value

Zhou

2021

Clin Appl Thromb Hemost

View full text Add to dashboard Cite

show abstract

“…Our results mainly focused on the effect of miR-27-3p on Notch pathway in TNBC cells, and miR-27-3p could also regulate some other pathways important for the survival of cancer cells, e.g. MMP13, PPARg, Wnt3a, BTG2 or NOVA1 (50)(51)(52)(53)(54)(55). In addition to regulating the survival of malignant tumor cells, miR-27-3p may also modify cancer microenvironment by inhibiting fibroblast viability by targeting NOVA1 (55).…”

Section: Discussionmentioning

confidence: 99%

miR-27-3p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to the Antitumor Agent Olaparib by Targeting PSEN-1, the Catalytic Subunit of Γ-Secretase

et al. 2021

View full text Add to dashboard Cite

Olaparib has been used in the treatment of triple-negative breast cancer (TNBC) with BRCA mutations. In the present study, we demonstrated the effect of miR-27-3p on the γ-secretase pathway by regulating the sensitivity of TNBC cells to olaparib. miR-27-3p, a microRNA with the potential to target PSEN-1, the catalytic subunit of γ-secretase mediating the second step of the cleavage of the Notch protein, was identified by the online tool miRDB and found to inhibit the expression of PSEN-1 by directly targeting the 3’-untranslated region (3’-UTR) of PSEN-1. The overexpression of miR-27-3p inhibited the activation of the Notch pathway via the inhibition of the cleavage of the Notch protein, mediated by γ-secretase, and, in turn, enhanced the sensitivity of TNBC cells to the antitumor agent olaparib. Transfection with PSEN-1 containing mutated targeting sites for miR-27-3p or the expression vector of the Notch protein intracellular domain (NICD) almost completely blocked the effect of miR-27-3p on the Notch pathway or the sensitivity of TNBC cells to olaparib, respectively. Therefore, our results suggest that the miR-27-3p/γ-secretase axis participates in the regulation of TNBC and that the overexpression of miR-27-3p represents a potential approach to enhancing the sensitivity of TNBC to olaparib.

show abstract

“…Notably, PPARγ, a key nuclear transcription factor, was shown to play a role in neuroprotection after CNS injury was reported to be associated with neuroinflammation ( Li J. et al, 2020 ). In an in vitro animal study, PPARγ was identified as a therapeutic target due to its observed ability to induce microglial activation and increase the expression of inflammatory factors in MCAO rats ( Ye et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Underlying Mechanism and Active Ingredients of Tianma Gouteng Acting on Cerebral Infarction as Determined via Network Pharmacology Analysis Combined With Experimental Validation

et al. 2021

View full text Add to dashboard Cite

Cerebral infarction (CI), a common cerebrovascular disease worldwide, is caused by unknown factors common to many diseases, including hypokalemia, respiratory diseases, and lower extremity venous thrombosis. Tianma Gouteng (TMGT), a traditional Chinese Medicine (TCM) prescription, has been used for the clinical treatment of CI. In this study, high-performance liquid chromatography (HPLC) fingerprint analysis was used to detect and identify major chemical constituents of TMGT. TCMSP and BATMAN-TCM databases were used to screen for active TMGT constituent compounds, while the GeneCards database was used to screen for protein targets associated with CI. Next, GO and KEGG enrichment analysis of these core nodes were performed to determine the identities of key associated biological processes and signal pathways. Meanwhile, a total of six possible gene targets of TMGT, including NFKBIA, PPARG, IL6, IL1B, CXCL8, and HIF1A, were selected for further study using two cellular models of CI. For one model, PC12 cells were treated under oxygen and glucose deprivation (OGD) conditions to generate an OGD cellular model of CI, while for the other model, BV2 cells were stimulated with lipopolysaccharide (LPS) to generate a cellular model of CI-associated inflammation. Ultimately TMGT treatment increased PPARγ expression and downregulated the expression of p-P65, p-IκBα, and HIF-1α in both OGD-induced and LPS-induced cell models of CI. In addition, molecular docking analysis showed that one TMGT chemical constituent, quercetin, may be a bioactive TMGT compound with activity that may be associated with the alleviation of neuronal damage and neuroinflammation triggered by CI. Moreover, additional data obtained in this work revealed that TMGT could inhibit neuroinflammation and protect brain cells from OGD-induced and LPS-induced damage by altering HIF-1α/PPARγ/NF-κB pathway functions. Thus, targeting this pathway through TMGT administration to CI patients may be a strategy for alleviating nerve injury and neuroinflammation triggered by CI.

show abstract

Serum Exosomal microRNA-27-3p Aggravates Cerebral Injury and Inflammation in Patients with Acute Cerebral Infarction by Targeting PPARγ

Cited by 30 publications

References 49 publications

miR-124 Is Downregulated in Serum of Acute Cerebral Infarct Patients and Shows Diagnostic and Prognostic Value

miR-124 Is Downregulated in Serum of Acute Cerebral Infarct Patients and Shows Diagnostic and Prognostic Value

miR-27-3p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to the Antitumor Agent Olaparib by Targeting PSEN-1, the Catalytic Subunit of Γ-Secretase

Underlying Mechanism and Active Ingredients of Tianma Gouteng Acting on Cerebral Infarction as Determined via Network Pharmacology Analysis Combined With Experimental Validation

Contact Info

Product

Resources

About