miR-31 shuttled by halofuginone-induced exosomes suppresses MFC-7 cell proliferation by modulating the HDAC2/cell cycle signaling axis |
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Authors: | Xiaojing Xia Xin Wang Shouping Zhang Yi Zheng Lei Wang Yanzhao Xu Bolin Hang Yawei Sun Liancheng Lei YueYu Bai Jianhe Hu |
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Institution: | 1. College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang, China;2. College of Agriculture and Forestry Science, Linyi University, Linyi, China;3. College of Basic Medical Sciences, Shandong University, Ji'nan, China;4. College of Veterinary Medicine, Jilin University, Changchun, China;5. Animal Health Supervision of Henan Province, Bureau of Animal Husbandry of Henan province, Zhengzhou, China |
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Abstract: | Traditional Chinese medicine (TCM) are both historically important therapeutic agents and important source of new drugs. Halofuginone (HF), a small molecule alkaloid derived from febrifugine, has been shown to exert strong antiproliferative effects that differ markedly among various cell lines. However, whether HF inhibits MCF-7 cell growth in vitro and underlying mechanisms of this process are not yet clear. Here, we offer the strong evidence of the connection between HF treatment, exosome production and proliferation of MCF-7 cells. Our results showed that HF inhibits MCF-7 cell growth in both time- and dose-dependent manner. Further microRNA (miRNA) profiles analysis in HF treated and nontreated MCF-7 cell and exosomes observed that six miRNAs are particularly abundant and sorted in exosomes. miRNAs knockdown experiment in exosomes and the MCF-7 growth inhibition assay showed that exosomal microRNA-31 (miR-31) modulates MCF-7 cells growth by specially targeting the histone deacetylase 2 (HDAC2), which increases the levels of cyclin-dependent kinases 2 (CDK2) and cyclin D1 and suppresses the expression of p21. In conclusion, these data indicate that inhibition of exosome production reduces exosomal miR-31, which targets the HDAC2 and further regulates the level of cell cycle regulatory proteins, contributing to the anticancer functions of HF. Our data suggest a new role for HF and the exosome production in tumorigenesis and may provide novel insights into prevention and treatment of breast cancer. |
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Keywords: | cell cycle exosome halofuginone HDAC2 MCF-7 miR-31 |
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