miRNAs as Modulators of Angiogenesis

Landskroner-Eiger, Shira; Moneke, Isabelle; Sessa, William C.

doi:10.1101/cshperspect.a006643

Cited by 157 publications

(121 citation statements)

References 86 publications

(133 reference statements)

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“…Previous studies have identified the miR-17/92 cluster, let-7 family and miR-145 as the modulators of angiogenesis [41]. The validated targets of the miR-17/92 cluster include TSP-1, CTGF, TIMP-1 and ITG5a.…”

Section: Discussionmentioning

confidence: 99%

Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation

et al. 2014

J Hematol Oncol

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BackgroundDysregulated microRNA (miRNA) expression contributes to cancer cell proliferation, apoptosis and angiogenesis. Angiogenesis is a hallmark of multiple myeloma (MM) development and progression. Argonaute 2 (AGO2) protein, a core component of the RNA-induced silencing complex (RISC), can directly bind to miRNAs and mediate target messenger RNA (mRNA) degradation. A previous study showed that AGO2 knockdown suppressed human umbilical vein endothelial cell (HUVEC) growth and tube formation. However, the roles and molecular mechanisms of AGO2-induced myeloma angiogenesis are not yet fully understood. The aim of this study was to characterize these roles and effects and their associated mechanisms.ResultsSupernatants from AGO2-overexpressing MM lines induced HUVEC migration and accelerated tube formation. Conversely, supernatants from AGO2-knockdown MM lines suppressed HUVEC cell migration and tube formation. Moreover, a chick chorioallantoic membrane (CAM) assay was used to demonstrate that AGO2 could drive neovessel formation in MM lines in vivo. Using an miRNA microarray, we observed that 25 miRNAs were upregulated and 7 were downregulated in response to AGO2. Most let-7 family members and 2 miR-17/92 cluster members (miR-17a and miR-92-1), all known pro-angiogenic miRNAs, were positively regulated by AGO2 whereas anti-angiogenic miRNAs such as miR-145 and miR-361 were negatively regulated by AGO2.ConclusionsWe conclude that AGO2 can drive neovessel formation in vitro and in vivo by dysregulating the expression of some angiogenic miRNAs. The pro-angiogenic miRNAs of the let-7 family and the miR-17/92 cluster, along with the anti-angiogenic miRNA miR-145, play crucial roles in AGO2-mediated angiogenesis by targeting angiogenesis-related genes.

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Section: Discussionmentioning

confidence: 99%

Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation

et al. 2014

J Hematol Oncol

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“…Park et al [98] demonstrated that melatonin suppresses tumor angiogenesis by inhibiting HIF-1 and VEGF via sphingosine kinase 1 in colon cancer cells. On the other hand, miRNAs play critical roles as modulators of angiogenesis [99]; e.g., overexpression of miRNA 3195 and miRNA 374b inhibits mRNA expression of HIF-1alpha, HIF-2alpha, and VEGF in hypoxia in prostate cancer cells, melatonin enhancing the expression of these miRNAs [100]. Therefore, the anti-angiogenic activity of melatonin can be the result of suppressing of HIF-1alpha by miRNA.…”

Section: Anti-angiogenic Activitymentioning

confidence: 99%

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

Cardinali¹,

Escames²,

Acuña-Castroviejo³

et al. 2016

J Integr Oncol

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“…Indeed, it has been proposed that EC death is one of the critical determinants of radiation damage34, a key therapeutic modality in cancer treatment. Since miRs influence several aspects of endothelial function5, we hypothesized that miRs regulate endothelial apoptosis in response to radiation damage. We have identified a microRNA (miR) signature in ECs induced in common by genotoxic stress, oxidative stress and DNA damage.…”

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confidence: 99%

MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment

et al. 2016

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Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of function approaches, we show that miR-103 exacerbates DNA damage and inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour growth. Mechanistically, miR-103 regulation of its target gene TREX1 in endothelial cells governs the secretion of pro-inflammatory cytokines into the tumour microenvironment. Our data suggest that this inflammatory milieu may potentiate tumour cell death by supporting immune activation and inducing tumour expression of Fas and TRAIL receptors. Our findings reveal miR-mediated crosstalk between vasculature and tumour cells that can be exploited to improve the efficacy of chemotherapy and radiation.

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miRNAs as Modulators of Angiogenesis

Cited by 157 publications

References 86 publications

Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation

Argonaute 2 promotes myeloma angiogenesis via microRNA dysregulation

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment

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