Abstract
Colorectal cancer (CRC) is one of the most prevalent cancers globally and is one of the leading causes of cancer-related deaths due to therapy resistance and metastasis. Understanding the mechanism underlying colorectal carcinogenesis is essential for the diagnosis and treatment of CRC. microRNAs (miRNAs) can act as either oncogenes or tumor suppressors in many cancers. A tumor suppressor role for miR-27b has recently been reported in neuroblastoma, while no information about miR-27b in CRC is available. In this study, we demonstrated that miR-27b expression is decreased in most CRC tissues and determined that overexpression of miR-27b represses CRC cell proliferation, colony formation and tumor growth in vitro and in vivo. We identified vascular endothelial growth factor C (VEGFC) as a novel target gene of miR-27b and determined that miR-27b functioned as an inhibitor of tumor progression and angiogenesis through targeting VEGFC in CRC. We further determined that DNA hypermethylation of miR-27b CpG islands decreases miR-27b expression. In summary, an anti-tumor role for miR-27b and its novel target VEGFC in vivo could lead to tumor necrosis and provide a rationale for developing miR-27b as a therapeutic agent.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Cell Line, Tumor
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Cell Proliferation
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology
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Colorectal Neoplasms / blood supply*
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Colorectal Neoplasms / genetics
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Colorectal Neoplasms / pathology*
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DNA Methylation / genetics
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Disease Progression*
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Mice
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Mice, SCID
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Molecular Sequence Data
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Neovascularization, Pathologic / genetics*
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Neovascularization, Pathologic / pathology
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Vascular Endothelial Growth Factor C / metabolism*
Substances
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MIRN27 microRNA, human
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MicroRNAs
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VEGFC protein, human
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Vascular Endothelial Growth Factor C
Grants and funding
This work was supported by grants from the National Natural Science Foundation of China (No. 91019005), Zhejiang Provincial Natural Science Foundation of China (No. Y2110034), the 151 Talent Project of Zhejiang Province (HJ) and the Science and Technology Bureau of Zhejiang Province (No. 2011C37004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.