Abstract
MicroRNAs, a kind of small non-coding RNAs, can regulate gene expression by targeting mRNAs for translational repression or degradation. Much evidence has suggested that miR-218 was a tumor suppressor in many human cancers including prostate cancer. However, the underlying role of miR-218 in tumor angiogenesis and the mechanisms in PCa and other cancers remains to be unclear. Here in this present study, we demonstrated that miR-218 inhibited the tumor angiogenesis of PCa cells in vitro and in vivo. RICTOR, the mTOR component 2, was a direct target of miR-218 and miR218-RICTOR-VEGFA axis was the mechanism inhibiting the tumor angiogenesis of PCa cells. RICTOR knockdown phenocopied miR-218 overexpression in inhibiting prostate cancer angiogenesis. Altogether, our findings indicate that down-regulation of miR-218 contributes to tumor angiogenesis through RICTOR/VEGFA axis in PCa, providing new insights into the potential mechanisms of PCa oncogenesis and revealing the potential of miR-218 as a useful serum biomarker and a new therapeutic target for human PCa.
Keywords:
RICTOR; VEGFA; angiogenesis; microRNA-218; prostate cancer.
MeSH terms
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3' Untranslated Regions
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Animals
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Binding Sites
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Gene Expression Regulation, Neoplastic
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HEK293 Cells
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Human Umbilical Vein Endothelial Cells / metabolism
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Male
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Mice, Nude
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Neovascularization, Pathologic*
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Phosphorylation
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism*
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Prostatic Neoplasms / pathology
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RNA Interference
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Rabbits
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Rapamycin-Insensitive Companion of mTOR Protein / genetics
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Rapamycin-Insensitive Companion of mTOR Protein / metabolism*
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Signal Transduction
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism*
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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3' Untranslated Regions
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Basic Helix-Loop-Helix Transcription Factors
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Biomarkers, Tumor
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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MIRN218 microRNA, human
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MicroRNAs
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RICTOR protein, human
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Rapamycin-Insensitive Companion of mTOR Protein
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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endothelial PAS domain-containing protein 1
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MTOR protein, human
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TOR Serine-Threonine Kinases