miR-31 shuttled by halofuginone-induced exosomes suppresses MFC-7 cell proliferation by modulating the HDAC2/cell cycle signaling axis.
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.
['Xia|Xiaojing|X|0000-0001-7717-8411', 'Wang|Xin|X|', 'Zhang|Shouping|S|', 'Zheng|Yi|Y|', 'Wang|Lei|L|', 'Xu|Yanzhao|Y|', 'Hang|Bolin|B|', 'Sun|Yawei|Y|', 'Lei|Liancheng|L|', 'Bai|YueYu|Y|', 'Hu|Jianhe|J|']
D000970:Antineoplastic Agents D001943:Breast Neoplasms D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D019938:Cyclin D1 D051357:Cyclin-Dependent Kinase 2 D050759:Cyclin-Dependent Kinase Inhibitor p21 D055354:Exosomes D005260:Female D056464:Histone Deacetylase 2 D006801:Humans D061986:MCF-7 Cells D008516:Medicine, Chinese Traditional D035683:MicroRNAs D010880:Piperidines D052999:Quinazolinones
miR-31 exosome HDAC2 cell cycle halofuginone MCF-7