Analysis of microRNA expression profiles in exosomes derived from acute myeloid leukemia by p62 knockdown and effect on angiogenesis

PeerJ

article

Chuan Li¹  Xinyi Long¹  Peiqi Liang²  Zhuogang Liu¹  Chen Wang¹  Rong Hu¹ 

[1] Hematology Department, Shengjing Hospital of China Medical University;Hematology Department, The First Affiliated Hospital of Suzhou University

关键词: Exosome;    microRNA;    Acute myeloid leukemia;    P62;    Angiogenesis;   

DOI  :  10.7717/peerj.13498

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

ObjectivesIn this study, we aimed to investigate the effect of p62 on angiogenesis and microRNA (miRNA) expression profiles in acute myeloid leukemia (AML) exosomes.MethodsAn Exiqon v19.0 microRNA MicroArray was used to profile miRNAs in exosomes derived from parental and p62-knockdown U937 cells. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict the biological functions and potential mechanisms of differentially expressed miRNAs in AML exosomes. Endothelial cell tube formation assays using human umbilical vein endothelial cells (HUVECs) were performed to investigate the effect of AML exosomes on angiogenesis.ResultsWe demonstrated that 2,080 miRNAs were expressed in exosomes derived from our cultured cell samples, of which 215 and 208 miRNAs were upregulated and downregulated, respectively, in p62-knockdown U937 cells (fold change ≥ 2, P < 0.05). GO analysis indicated that miRNAs were most enriched in the intercellular pathways. Biological process analysis revealed that 1460 biological processes were associated with downregulated transcripts, including 19 pathways related to vesicles, and 1,515 pathways were upregulated, including 8 pathways related to vesicles. Molecular function analysis indicated that protein binding, transcription regulator activity, and DNA-binding transcription factor activity were enriched (P < 0.05). Pathway analysis indicated that 84 pathways corresponded to upregulated transcripts, and 55 pathways corresponded to downregulated transcripts (P < 0.05). We also found that exosomes derived from U937 cells promoted angiogenesis in HUVECs.ConclusionsOur data suggest that exosomal miRNAs may play important roles in the pathogenesis of AML, which may be treated by p62 knockdown with exosomal miRNAs to inhibit angiogenesis.

【 授权许可】

CC BY