Analysis of miRNA signature differentially expressed in exosomes from adriamycin-resistant and parental human breast cancer cells

摘要

A major cause of failure in chemotherapy is drug resistance of cancer cells. Exosomes have been introduced to spread chemoresistance through delivering miRNAs. However, a systematic evaluation of the exosomal miRNA expression profiles responsible for chemoresistance is still lacking. In the present study, miRNA signature differentially expressed in exosomes derived from adriamycin-resistant (A/exo) and parental breast cancer cells (S/exo) were analyzed by microarray and the results were confirmed by PCR. A total of 309 miRNAs were increased and 66 miRNAs were decreased significantly in A/exo compared with S/exo. Specifically, 52 novel miRNAs with increased expression levels >16.0-fold in A/exo were identified. After prediction of target genes for 13 of 52 selected novel miRNAs, pathway analysis, gene ontology (GO) terms, and protein–protein interactions (PPIs) were constructed. The results implied that these selected exosomal miRNAs inhibited target genes involved in transcriptional misregulation in cancer, MAPK, and Wnt signaling pathways. Functional enrichment analysis demonstrated that the target genes were mainly responsible for protein phosphorylation, transcription regulation, molecular binding, and kinase activity. In summary, the current bioinformatics study of exosomal miRNAs may offer a new understanding into mechanisms of chemoresistance, which is helpful to find potential exosomal miRNAs to overcome drug insensitivity in future breast cancer treatment.