Aberrant Expression of Mir-20a in Serum Exosomes of Multiple Myeloma Lead Abnormal Expression of HIF-1 Signaling Pathway Related Proteins

Objective To determine the abnormal expression of miRNA in plasma exosomes of patients with multiple myeloma (MM) and its effect on the expression of HIF signaling pathway related proteins.

Methods Microarray analysis was performed on the exosomal miRNA analysis of 12 MM patients to determine how it might participate in MM. Then a co-expression network was performed to discover the potential role of miRNAs in regulating tumorigenesis and disease progression of MM. The expression of miR-20a in the exosomes of 48 MM patients was detected and the potential target genes were verified.

Results Differential expression of 43 miRNAs was observed in exosomes of multiple myeloma (MM) patients compared to healthy individuals. Among them, 7 miRNAs were significantly up-regulated in patients with multiple myeloma, and 35 miRNAs were significantly decreased compared with healthy controls. The results of microarray analysis showed that the seven miRNAs up-regulated in MM exosomes were mainly involved in NF-κB signaling, tumor necrosis factor-mediated signaling pathway regulation while 37 down-regulated miRNAs are mainly involved in HIF-1 signaling pathway, vascular development, cell adhesion. Decreased expression of miR-20a was associated with MM aggressiveness in the MM cohort compared with healthy individuals. We identified HIF-1 signaling pathway related proteins SENP1 and sumo as a potential target gene of miR-20a which were upregulation in MM.

Conclusion The microarray chip confirmed the differential expression of miRNA in plasma exosomes of patients with myeloma and healthy controls. Abnormally expressed miRNAs may be involved in the occurrence and development of tumors. These results may provide further evidence for exosomes as novel biomarkers for predicting MM recurrence.