Dataset Information

MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells.

ABSTRACT:

Background

MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the control of angiogenesis renders them very attractive in the development of new approaches for restoring the angiogenic balance. Whereas miRNA-21 has been demonstrated to be highly expressed in endothelial cells, the potential function of this miRNA in angiogenesis has never been investigated.

Methodology/principal findings

We first observed in endothelial cells a negative regulation of miR-21 expression by serum and bFGF, two pro-angiogenic factors. Then using in vitro angiogenic assays, we observed that miR-21 acts as a negative modulator of angiogenesis. miR-21 overexpression reduced endothelial cell proliferation, migration and the ability of these cells to form tubes whereas miR-21 inhibition using a LNA-anti-miR led to opposite effects. Expression of miR-21 in endothelial cells also led to a reduction in the organization of actin into stress fibers, which may explain the decrease in cell migration. Further mechanistic studies showed that miR-21 targets RhoB, as revealed by a decrease in RhoB expression and activity in miR-21 overexpressing cells. RhoB silencing impairs endothelial cell migration and tubulogenesis, thus providing a possible mechanism for miR-21 to inhibit angiogenesis. Finally, the therapeutic potential of miR-21 as an angiogenesis inhibitor was demonstrated in vivo in a mouse model of choroidal neovascularization.

Conclusions/significance

Our results identify miR-21 as a new angiogenesis inhibitor and suggest that inhibition of cell migration and tubulogenesis is mediated through repression of RhoB.

SUBMITTER: Sabatel C

PROVIDER: S-EPMC3037403 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells.

Sabatel Céline C Malvaux Ludovic L Bovy Nicolas N Deroanne Christophe C Lambert Vincent V Gonzalez Maria-Luz Alvarez ML Colige Alain A Rakic Jean-Marie JM Noël Agnès A Martial Joseph A JA Struman Ingrid I

PloS one 20110210 2

<h4>Background</h4>MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the control of angiogenesis renders them very attractive in the development of new approaches for restoring the angiogenic balance. Whereas miRNA-21 has been demonstrated to be highly expressed in endothelial cells, the potential function of this miRNA in angiogenesis has never been investigate ...[more]

PMID: 21347332

Similar Datasets

Project description:Rationale & objectivePrevious studies have suggested that microRNA-21 (miR-21) plays an important role in kidney fibrosis. We examined the relationship between intrarenal miR-21 level and rate of kidney function loss in immunoglobulin A nephropathy (IgAN).Study designProspective cohort study.Setting & participants40 patients with IgAN and 10 with hypertensive nephrosclerosis as controls.PredictorsmiR-21 levels in kidney biopsy specimen and urinary sediment, quantified as ratio to the housekeeping gene.OutcomesKidney event-free survival and rate of kidney function decline.Analytic approachTime-to-event and correlation analysis.ResultsThe IgAN group had significantly higher intrarenal miR-21 expression compared with the hypertensive nephrosclerosis group (1.71 [IQR, 0.99-2.77] vs 0.31 [IQR, 0.25-1.32]; P < 0.0001), but urinary miR-21 levels were similar. Intrarenal miR-21 expression had significant but modest correlation with severity of glomerulosclerosis (r = 0.293; P = 0.05) and tubulointerstitial fibrosis (r = 0.341; P = 0.03). Patients with high intrarenal miR-21 expression had significantly higher risk for developing kidney end points compared with those with low expression (log-rank test, P = 0.017). Univariate Cox analysis showed that intrarenal miR-21 expression significantly predicted the development of kidney end points (unadjusted HR, 1.586; 95% CI, 1.179-2.134; P = 0.002). However, the result was just short of statistical significance after adjusting for the severity of histologic damage (P = 0.06). There was also a significant correlation between intrarenal miR-21 expression and the slope of kidney function decline by univariate analysis (r = -0.399; P = 0.02).LimitationsSmall sample size; uncertain cellular origin of miR-21.ConclusionsWe found that intrarenal miR-21 expression is increased in patients with IgAN, modestly correlated with the severity of histologic damage, and predictive of subsequent kidney function loss.

Dataset Information

MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells.

Background

Methodology/principal findings

Conclusions/significance

Publications

MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets