Commitment of Annexin A2 in recruitment of microRNAs into extracellular vesicles

•ANXA2 silencing is highly efficient for decreasing EV miRNA abundance.•Overexpression of ANXA2 increases the total amount of miRNAs in EVs.•ANXA2 regulates EV miRNA loading in a sequence independent manner.•ANXA2 binds miRNAs in EVs in the presence of Ca2+.•This is the first evidence describing the...

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Bibliographic Details
Published in:FEBS letters 2015-12, Vol.589 (24), p.4071-4078
Main Authors: Hagiwara, Keitaro, Katsuda, Takeshi, Gailhouste, Luc, Kosaka, Nobuyoshi, Ochiya, Takahiro
Format: Article
Language:English
Subjects:
Annexin
Annexin A1
Annexin A2
Annexin A2 - antagonists & inhibitors
Annexin A2 - genetics
Annexin A2 - metabolism
Annexin A5
Annexin A5 - antagonists & inhibitors
Annexin A5 - genetics
Annexin A5 - metabolism
Annexin A6
ANXA1
ANXA2
ANXA5
ANXA6
Biological Transport
Calcium Signaling
Cancer
Cell Line, Tumor
EEF1G
EEF2
elongation factor 1-γ
elongation factor 2
Extracellular vesicle
Extracellular Vesicles - metabolism
GAPDH
Gene Expression Regulation, Neoplastic
glyceraldehyde 3-phosphate dehydrogenase
HIST4H4
histone H4
Humans
Immunoprecipitation
MicroRNA
MicroRNAs - chemistry
MicroRNAs - metabolism
miRNA
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Oligonucleotide Array Sequence Analysis
Particle Size
Proteomic
Proteomics - methods
qRT-PCR
quantitative RT-PCR
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - metabolism
ribonuclease
RNA Interference
RNA, Neoplasm - chemistry
RNA, Neoplasm - metabolism
RNA, Small Interfering
RNase
siRNA
small interference RNA
Small interfering RNA
Up-Regulation
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Summary:•ANXA2 silencing is highly efficient for decreasing EV miRNA abundance.•Overexpression of ANXA2 increases the total amount of miRNAs in EVs.•ANXA2 regulates EV miRNA loading in a sequence independent manner.•ANXA2 binds miRNAs in EVs in the presence of Ca2+.•This is the first evidence describing the loading process of miRNAs into EVs. 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 Ca2+. These observations demonstrate that ANXA2 plays an important role in the packaging process of miRNAs into EVs.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2015.11.036