MicroRNA-126-3p suppresses cell proliferation by targeting PIK3R2 in Kaposi's sarcoma cells

Wu, Xiujuan; Zhao, Zhiyao; Kang, Xiaojian; Wang, Hongjuan; Zhao, Juan; Pu, Xiongming

doi:10.18632/oncotarget.9311

Cited by 17 publications

(18 citation statements)

References 35 publications

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“…Pathway analysis showed that cell adhesion molecules were significantly regulated by both miR-126-3p and miR-126-5p. MiR-126-3p transfection significantly decreased PIK3R2 mRNA levels, which is a known target of miR-126-3p [22] (Table 1). MiR-126-5p similarly significantly decreased its targets high-mobility group protein (HMGB)1 and vascular endothelial growth factor (VEGF)α (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury

et al. 2019

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BackgroundThe acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar-capillary barrier resulting in accumulation of proteinaceous edema and increased inflammatory cells in the alveolar space. We previously found that endothelial progenitor cell (EPC) exosomes prevent endothelial dysfunction and lung injury in sepsis in part due to their encapsulation of miRNA-126. However, the effects of EPC exosomes in acute lung injury (ALI) remain unknown.MethodsTo determine if EPC exosomes would have beneficial effects in ALI, intratracheal administration of lipopolysaccharide (LPS) was used to induce ALI in mice. Lung permeability, inflammation, and the role of miRNA-126 in the alveolar-epithelial barrier function were examined.ResultsThe intratracheal administration of EPC exosomes reduced lung injury following LPS-induced ALI at 24 and 48 h. Compared to placebo, intratracheal administration of EPC exosomes significantly reduced the cell number, protein concentration, and cytokines/chemokines in the bronchoalveolar lavage fluid (BALF), indicating a reduction in permeability and inflammation. Further, EPC exosomes reduced myeloperoxidase (MPO) activity, lung injury score, and pulmonary edema, demonstrating protection against lung injury. Murine fibroblast (NIH3T3) exosomes, which do not contain abundant miRNA-126, did not provide these beneficial effects. In human small airway epithelial cells (SAECs), we found that overexpression of miRNA-126-3p can target phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), while overexpression of miRNA-126-5p inhibits the inflammatory alarmin HMGB1 and permeability factor VEGFα. Interestingly, both miR-126-3p and 5p increase the expression of tight junction proteins suggesting a potential mechanism by which miRNA-126 may mitigate LPS-induced lung injury.ConclusionsOur data demonstrated that human EPC exosomes are beneficial in LPS-induced ALI mice, in part through the delivery of miRNA-126 into the injured alveolus.Electronic supplementary materialThe online version of this article (10.1186/s13054-019-2339-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury

et al. 2019

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“…To assess whether miR-126-3p was able to regulate these putative target genes, we transfected the T-cell leukemia cell line Jurkat with a miR-126-3p mimic and we evaluated the impact of its ectopic expression on AKT2 , PPP3CB , RANKL, and SDC2 transcript levels. We used PIK3R2 as positive control of the miRNA mimic, since it is a well-known miR-126-3p target [ 30 ]. After 48 hours from transfection, miR-126-transfected cells expressed significantly lower levels of all the targets as compared to the mimic control ( Figure 5(d) ).…”

Section: Resultsmentioning

confidence: 99%

MicroRNA Expression Profiling in Psoriatic Arthritis

Pelosi

Lunardi

Fiore

et al. 2018

BioMed Research International

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Background Psoriatic arthritis (PsA) is an inflammatory arthritis, characterized by bone erosions and new bone formation. MicroRNAs (miRNAs) are key regulators of the immune responses. Differential expression of miRNAs has been reported in several inflammatory autoimmune diseases; however, their role in PsA is not fully elucidated. We aimed to identify miRNA expression signatures associated with PsA and to investigate their potential implication in the disease pathogenesis. Methods miRNA microarray was performed in blood cells of PsA patients and healthy controls. miRNA pathway analyses were performed and the global miRNA profiling was combined with transcriptome data in PsA. Deregulation of selected miRNAs was validated by real-time PCR. Results We identified specific miRNA signatures associated with PsA patients with active disease. These miRNAs target pathways relevant in PsA, such as TNF, MAPK, and WNT signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the PsA transcriptome. miR-126-3p was the most downregulated miRNA in active patients. Noteworthy, miR-126 overexpression induced a decreased expression of genes implicated in PsA. Conclusions This study sheds light on some epigenetic aspects of PsA identifying specific miRNAs, which may represent promising candidates as biomarkers and/or for the design of novel therapeutic strategies in PsA.

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“…Chen et al ( 46 ) demonstrated that miR-126-3p was associated with advanced pathological stage and lymph node metastasis in patients with lung adenocarcinoma. miR-126-3p is the most endothelial-specific miRNA that alters vascular integrity and angiogenesis, and it served as a tumor inhibitor targeting phophoinositide-3-kinase regulatory subunit 2 in Kaposi's sarcoma cells ( 47 ). Its expression appeared to be upregulated in colon cancer, as demonstrated by Ji et al ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic microRNAs and their potential molecular mechanism in pancreatic cancer: A study based on The Cancer Genome Atlas and bioinformatics investigation

Liang

Wei

et al. 2017

Mol Med Report

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Although certain biomarkers that are directly associated with the overall survival (OS) of patients with pancreatic adenocarcinoma (PAAD) have been identified, the efficacy of a single factor is limited to predicting the prognosis. The aim of the present study was to identify a combination micro (mi)RNA signature that enhanced the prognostic prediction for PAAD. Following analysis of the data available from The Cancer Genome Atlas (TCGA), 175 PAAD samples were selected for the present study, and the associations between 494 miRNAs and OS were investigated. The prognostic value of all miRNAs was analyzed by multivariate Cox regression, and the miRNAs were ranked according to the hazard ratio (HR) and P-values. The top 5 miRNAs (miR-1301, miR-125a, miR-376c, miR-328 and miR-376b) were significantly associated with OS (HR=0.139; 95% confidence interval, 0.043–0.443; P<0.001), thus demonstrating that this panel was able to serve as an independent prognostic factor for PAAD. In addition, the present study also predicted the target genes of the top 10 miRNAs with the highest prognostic values using 12 different prediction software, and enrichment signaling pathway analyses elucidated that several pathways may be markedly associated with these miRNAs, including ‘Pathways in cancer’, ‘Chronic myeloid leukemia’, ‘Glioma’ and ‘MicroRNAs in cancer’. Lastly, ubiquitin C, epidermal growth factor receptor, estrogen receptor 1, mitogen-activated protein kinase 1, mothers against decapentaplegic homolog 4 and androgen receptor may be the hub genes revealed by STRING analysis. The present study identified several miRNAs, particularly a five-miRNA-pool, that may be reliable, independent factors for predicting survival in patients with PAAD. However, the underlying molecular mechanisms require further investigation in the future.

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MicroRNA-126-3p suppresses cell proliferation by targeting PIK3R2 in Kaposi's sarcoma cells

Cited by 17 publications

References 35 publications

Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury

Exosomes from endothelial progenitor cells improve outcomes of the lipopolysaccharide-induced acute lung injury

MicroRNA Expression Profiling in Psoriatic Arthritis

Prognostic microRNAs and their potential molecular mechanism in pancreatic cancer: A study based on The Cancer Genome Atlas and bioinformatics investigation

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