Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNAMeg3/miR421/PDGFRA axis.
Int J Oncol
; 55(6): 1296-1312, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-31638182
ABSTRACT
Angiogenesis has an important role in tumour cell growth and metastasis. Anisomycin has been shown to inhibit tumour cell growth. However, whether anisomycin can inhibit angiogenesis of tumours has not been reported. The present study demonstrated that there was a positive correlation between tumour angiogenesis and the number of CD44+/CD133+ serous human ovarian cancer stem cells (HuOCSCs). Subsequently, it was confirmed that anisomycin significantly inhibited the proliferation, invasion, tumorigenic ability and tumour angiogenesis of HuOCSCs. Gene expression profiling by cDNA microarrays revealed that the expression levels of vascular endothelial cell markers, plateletderived growth factors, Notch pathway components and 27 tumour angiogenesisrelated genes were significantly decreased in the anisomycintreated group compared with the control group. Further experiments demonstrated that the expression levels of endogenous long noncoding RNA (lncRNA) maternally expressed 3 (Meg3) were significantly decreased in anisomycintreated HuOCSCs, whereas the expression levels of microRNA (miR)421 were significantly increased. The results of luciferase reporter assays indicated that, when miR421 was overexpressed in cells, the luciferase activities of wildtype platelet derived growth factor receptor α (PDGFRA) 3' untranslated region and Meg3 reporter plasmids were significantly decreased. Overexpression of miR421 in HuOCSCs significantly enhanced the anisomycinmediated inhibition of HuOCSC proliferation. Taken together, the present results demonstrated that anisomycin inhibited the activation downstream of the Notch1 pathway by attenuating the molecular sponge effect of the lncRNAMeg3/miR421/PDGFRA axis, ultimately inhibiting angiogenesis, proliferation and invasion in ovarian cancer cells.
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MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Regulação Neoplásica da Expressão Gênica
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Carcinoma Epitelial do Ovário
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Anisomicina
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Neovascularização Patológica
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article