Regulation of tumor angiogenesis by microRNAs: State of the art

Goradel, Nasser Hashemi; Mohammadi, Naser; Haghi‐Aminjan, Hamed; Farhood, Bagher; Negahdari, Babak; Sahebkar, Amirhossein

doi:10.1002/jcp.27051

Cited by 89 publications

(61 citation statements)

References 138 publications

(194 reference statements)

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“…Angiogenesis (microvascular formation) is a cancer maker that provides substances necessary for tumour growth while removing waste and sediment from the tumour microenvironment. 53 In a previous study, in vitro capillary network formation experiments using HBMECs revealed that 10 μM ivermectin completely eliminated the ability of HBMECs to form tubular structures, confirming the effect of ivermectin against angiogenesis. 24 In conclusion, these findings indicate that ivermectin is a powerful angiogenesis inhibitor that also inhibits proliferation and induces apoptosis in HBMECs.…”

Section: Other Novel Molecular Mechanisms Of Ivermectin Ivermectin Ismentioning

confidence: 56%

“…24 Several miRNAs have been revealed to influence the expression of VEGF and its tyrosine kinase receptors downstream of hypoxiainducible factor 1 (HIF-1) in tumour angiogenesis. 53 Whether these miRNAs are targets of ivermectin remains to be confirmed, but the probable mechanisms have not been studied.…”

Section: Other Novel Molecular Mechanisms Of Ivermectin Ivermectin Ismentioning

confidence: 99%

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<p>Progress in Understanding the Molecular Mechanisms Underlying the Antitumour Effects of Ivermectin</p>

Liu

Zhang

Cheng

et al. 2020

DDDT

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Ivermectin, a dihydro derivative of avermectin (AVM), was introduced into the veterinary, agricultural and aquaculture markets for animal health in 1981. Ivermectin was soon adopted in 1987 as a human medicine that was originally used for the treatment of onchocerciasis, a parasitic infection. Since then, ivermectin has also been used to control other human diseases and has exerted a significant effect on human health and welfare. In the past decade, many published studies have attempted to determine the role of ivermectin in cancer. In this review, we summarize the published studies to define the current progress in the characterization of ivermectin. Ivermectin causes cell death in cancer cell lines by inducing PAK1-mediated cytostatic autophagy, caspase-dependent apoptosis and immunogenic cell death (ICD) through the modulation of some pathways, including the WNT-T cell factor (TCF), Hippo and Akt/ mTOR pathways. Ivermectin can affect the growth and proliferation of cancer cells and plays several different roles, such as its functions as an RNA helicase, a small-molecule mimetic of the surface-induced dissociation (SID) peptide, an activator of chloride channel receptors, and an inducer of mitochondrial dysfunction and oxidative stress. In addition, ivermectin induces the multidrug resistance protein (MDR), has potent anti-mitotic activity, targets angiogenesis and inhibits cancer stem-like cells (CSCs). Many studies have proven that ivermectin exerts antitumour effects and might thus benefit patients with cancer after sufficient clinical trials.

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Section: Other Novel Molecular Mechanisms Of Ivermectin Ivermectin Ismentioning

confidence: 56%

Section: Other Novel Molecular Mechanisms Of Ivermectin Ivermectin Ismentioning

confidence: 99%

<p>Progress in Understanding the Molecular Mechanisms Underlying the Antitumour Effects of Ivermectin</p>

Liu

Zhang

Cheng

et al. 2020

DDDT

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“…MiRNAs are increasingly being investigated as potential antiangiogenic small molecule drugs for tumor therapy (Goradel et al, 2019). In this study, bioinformatic analysis was used to identify miRNAs that could potentially target ALK1, and 12 candidate miRNAs were selected.…”

Section: Discussionmentioning

confidence: 99%

MiR-199b-5p Suppresses Tumor Angiogenesis Mediated by Vascular Endothelial Cells in Breast Cancer by Targeting ALK1

et al. 2020

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Angiogenesis is a crucial event during cancer progression that regulates tumor growth and metastasis. Activin receptor-like kinase 1 (ALK1), predominantly expressed in endothelial cells, plays a key role in the organization of neo-angiogenic vessels. Therapeutic targeting of ALK1 has been proposed as a promising strategy for cancer treatment, and microRNAs (miRNAs) are increasingly being explored as modulators of angiogenesis. However, the regulation of ALK1 by miRNAs is unclear. In this study, we identified that ALK1 is directly targeted by miR-199b-5p, which was able to inhibit angiogenesis in vitro and in vivo. Moreover, it was found that miR-199b-5p was repressed in breast cancer cells and its expression was decreased during the VEGFinduced angiogenesis process of human umbilical vein endothelial cells (HUVECs). Overexpression of miR-199b-5p inhibited the formation of capillary-like tubular structures and migration of HUVECs. Furthermore, overexpression of miR-199b-5p inhibited the mRNA and protein expression of ALK1 in HUVECs by directly binding to its 3'UTR. Additionally, overexpression of miR-199b-5p attenuated the induction of ALK1/ Smad/Id1 pathway by BMP9 in HUVECs. Finally, overexpression of miR-199b-5p reduced tumor growth and angiogenesis in in vivo. Taken together, these findings demonstrate the anti-angiogenic role of miR-199b-5p, which directly targets ALK1, suggesting that miR-199b-5p might be a potential anti-angiogenic target for cancer therapy.

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“…Among the regulators of tumor angiogenesis are microRNAs (miRNAs), which can act as anti-angiogenic but also as pro-angiogenic factors [6,7]. miRNAs are small (21-25 nucleotides) non-coding RNAs that negatively regulate gene expression [8].…”

Section: Introductionmentioning

confidence: 99%

Insights into the Regulation of Tumor Angiogenesis by Micro-RNAs

Leone

Buonavoglia

Fasano

et al. 2019

JCM

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One of the hallmarks of cancer is angiogenesis, a series of events leading to the formation of the abnormal vascular network required for tumor growth, development, progression, and metastasis. MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs whose functions include modulation of the expression of pro- and anti-angiogenic factors and regulation of the function of vascular endothelial cells. Vascular-associated microRNAs can be either pro- or anti-angiogenic. In cancer, miRNA expression levels are deregulated and typically vary during tumor progression. Experimental data indicate that the tumor phenotype can be modified by targeting miRNA expression. Based on these observations, miRNAs may be promising targets for the development of novel anti-angiogenic therapies. This review discusses the role of various miRNAs and their targets in tumor angiogenesis, describes the strategies and challenges of miRNA-based anti-angiogenic therapies and explores the potential use of miRNAs as biomarkers for anti-angiogenic therapy response.

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Regulation of tumor angiogenesis by microRNAs: State of the art

Cited by 89 publications

References 138 publications

<p>Progress in Understanding the Molecular Mechanisms Underlying the Antitumour Effects of Ivermectin</p>

<p>Progress in Understanding the Molecular Mechanisms Underlying the Antitumour Effects of Ivermectin</p>

MiR-199b-5p Suppresses Tumor Angiogenesis Mediated by Vascular Endothelial Cells in Breast Cancer by Targeting ALK1

Insights into the Regulation of Tumor Angiogenesis by Micro-RNAs

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