Hagiwara Keitaro, Katsuda Takeshi, Gailhouste Luc, Kosaka Nobuyoshi, Ochiya Takahiro
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; Department of Biochemistry and Molecular Pathophysiology, University of Occupational and Environmental Health, School of Medicine, Kitakyusyu, Fukuoka 807-8555, Japan.
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
FEBS Lett. 2015 Dec 21;589(24 Pt B):4071-8. doi: 10.1016/j.febslet.2015.11.036. Epub 2015 Nov 26.
Extracellular vesicles (EVs) contain microRNAs (miRNAs). However, the exact molecular mechanisms of the recruitment of miRNAs in EVs are not well characterized. Based on proteomic analysis, we identified that silencing of Annexin A2 (ANXA2) significantly decreased the amount of miRNAs in EVs. In addition, microarray analysis revealed that ANXA2 regulated the loading of miRNAs into EVs in a sequence independent manner. Lastly, immunoprecipitation analysis confirmed that ANXA2 could bind miRNAs in EVs in the presence of Ca(2+). These observations demonstrate that ANXA2 plays an important role in the packaging process of miRNAs into EVs.
细胞外囊泡(EVs)含有微小RNA(miRNAs)。然而,miRNAs被招募到EVs中的具体分子机制尚未得到充分表征。基于蛋白质组学分析,我们发现膜联蛋白A2(ANXA2)的沉默显著降低了EVs中miRNAs的含量。此外,微阵列分析表明,ANXA2以序列非依赖的方式调节miRNAs装载到EVs中。最后,免疫沉淀分析证实,在Ca(2+)存在的情况下,ANXA2可以与EVs中的miRNAs结合。这些观察结果表明,ANXA2在miRNAs包装到EVs的过程中起重要作用。