Dataset Information

MiR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells.

ABSTRACT: The miR-200 family plays a crucial role in epithelial to mesenchymal transition via controlling cell migration and polarity. We hypothesized that miR-200b, one miR-200 family member, could regulate angiogenic responses via modulating endothelial cell migration. Delivery of the miR-200b mimic in human microvascular endothelial cells (HMECs) suppressed the angiogenic response, whereas miR-200b-depleted HMECs exhibited elevated angiogenesis in vitro, as evidenced by Matrigel® tube formation and cell migration. Using in silico studies, miR target reporter assay, and Western blot analysis revealed that v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1), a crucial angiogenesis-related transcription factor, serves as a novel direct target of miR-200b. Knocking down endogenous Ets-1 simulated an anti-angiogenic response of the miR-200b mimic-transfected cells. Certain Ets-1-associated genes, namely matrix metalloproteinase 1 and vascular endothelial growth factor receptor 2, were negatively regulated by miR-200b. Overexpression of Ets-1 rescued miR-200b-dependent impairment in angiogenic response and suppression of Ets-1-associated gene expression. Both hypoxia as well as HIF-1? stabilization inhibited miR-200b expression and elevated Ets-1 expression. Experiments to identify how miR-200b modulates angiogenesis under a low oxygen environment illustrated that hypoxia-induced miR-200b down-regulation de-repressed Ets-1 expression to promote angiogenesis. This study provides the first evidence that hypoxia-sensitive miR-200b is involved in induction of angiogenesis via directly targeting Ets-1 in HMECs.

SUBMITTER: Chan YC

PROVIDER: S-EPMC3023502 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells.

Chan Yuk Cheung YC Khanna Savita S Roy Sashwati S Sen Chandan K CK

The Journal of biological chemistry 20101116 3

The miR-200 family plays a crucial role in epithelial to mesenchymal transition via controlling cell migration and polarity. We hypothesized that miR-200b, one miR-200 family member, could regulate angiogenic responses via modulating endothelial cell migration. Delivery of the miR-200b mimic in human microvascular endothelial cells (HMECs) suppressed the angiogenic response, whereas miR-200b-depleted HMECs exhibited elevated angiogenesis in vitro, as evidenced by Matrigel® tube formation and cel ...[more]

PMID: 21081489

Similar Datasets

Project description:BackgroundHypoxia is a hallmark of cancer and is associated with poor prognosis. However, the molecular mechanism by which hypoxia promotes tumor progression remains unclear. MicroRNAs dysregulation has been shown to play a critical role in the tumor and tumor microenvironment. Here, we investigated the roles of miR-495 and miR-5688 in human non-small cell lung cancer (NSCLC) and their underlying mechanism.MethodsThe expression levels of miR-495 and miR-5688 in human NSCLC tissue specimens were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Deferoxamine (DFO) was used to determine whether the regulation of miR-495 and miR-5688 under hypoxia was dependent on hypoxia-inducible factor 1-alpha (HIF-1α). Furthermore, the functions of miR-495 and miR-5688 in tumor progression were evaluated using colony formation, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), wound healing, transwell assays, and xenograft model. Two algorithms, PicTAR and Targetscan, were used to predict the target gene of these two miRNAs, and dual-luciferase reporter assay was conducted to confirm the target. The unpaired two-tailed t test, Pearson correlation analysis, and Fisher's exact probability test were performed for statistical analyses.ResultsTwo miRNAs, miR-495 and miR-5688, were found to participate in NSCLC progression under hypoxia. They were down-regulated in NSCLC tissues compared with normal tissues. We determined that hypoxia led to the down-regulation of miR-495 and miR-5688 in NSCLC cells, which was independent of HIF-1α and cellular metabolic energy. In addition, miR-495 and miR-5688 suppressed cell proliferation, migration, and invasion in vitro. The NSCLC xenograft model showed that miR-495 and miR-5688 inhibited tumor formation in vivo. Interestingly, we found that miR-495 and miR-5688 had the same target, interleukin-11 (IL-11). Recombinant human IL-11 counteracted the effects of miR-495 and miR-5688 on NSCLC cells, suggesting that miR-495 and miR-5688 executed their tumor suppressive role by repressing IL-11 expression.ConclusionWe found that hypoxia down-regulated the expression levels of miR-495 and miR-5688 in NSCLC to enhance IL-11 expression and tumor progression, indicating that the miR-495/miR-5688/IL-11 axis may serve as a therapeutic target and potential biomarker for NSCLC.

Dataset Information

MiR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells.

Publications

miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure