Abstract
MicroRNAs (miRNAs) have been suggested to play a vital role in regulate tumor progression and invasion. However, the expression of miR-339-5p in colorectal cancer and its effects are not known. Here, we report that miR-339-5p is a tumor suppressor by regulating expression of PRL-1. In this study, we showed that downregulated miR-339-5p levels in colorectal cancer tissues and highly invasive CRC cell lines. Furthermore, enhancing the expression of miR-339-5p inhibited CRC cell growth, migration and invasion in vitro and suppressed tumor growth in vivo. We then screened and identified a novel miR-339-5p target, phosphatases of regenerating liver-1 1 (PRL-1), and it was further confirmed by luciferase assay. Overexpression of miR-339-5p would also reduce the expression of PRL-1 mRNA and protein. The reduced PRL-1 expression was associated with low expression of phosphorylated-extracellular signal-regulated kinase1/2 (p-ERK1/2). Conversely, reduction of miR-339-5p by inhibitors in cells stimulated these phenotypes. In conclusion, our results demonstrate that miR-339-5p functions as a tumor suppressor and plays a role in inhibiting growth and metastasis of CRC cells through targeting PRL-1 and regulating p-ERK1/2 .These findings suggest that miR-339-5p may be useful as a new potential therapeutic target for CRC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / therapeutic use
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Blotting, Western
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Cell Cycle / drug effects
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Cell Cycle / genetics
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Colorectal Neoplasms / drug therapy
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Colorectal Neoplasms / genetics*
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Colorectal Neoplasms / metabolism*
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Colorectal Neoplasms / therapy
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / genetics
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Humans
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In Vitro Techniques
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics*
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Cell Cycle Proteins
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MIRN339 microRNA, human
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Membrane Proteins
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MicroRNAs
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PTP4A1 protein, human
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Protein Tyrosine Phosphatases
Grants and funding
The study is supported by National Natural Science Foundation of China (No 30871156, No 81272758), Science and Technology Project of Guangdong Province (2009B030803041), and Natural Science Foundation of Guangdong Province (No 8151051501000057). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.