[Expression of miR-550a-5p in Myelodysplastic Syndrome and Its Prediction of Target Genes].

OBJECTIVE: To investigate the expression of miR-550a-5p in bone marrow of patients with myelodysplastic syndrome (MDS), and to predict its target genes and function by bioinformatics analyses, so as to provide the evidence to furthre explore the role of miR-550a-5p and its target genes in pathogenesis of MDS.

METHODS: Real-time PCR was used to detect the expression of miR-550a-5p in 54 MDS patients, 16 acute myeloid leukemia transformed from MDS (sfAML) and 19 healthy controls, and the correlation between the expression of miR-550a-5p and clinical pathologic characteristics of MDS, including chromosome, percentage of marrow blasts, absolute neutrophil count, platelet count and hemoglobin levels were analyzed. The sequence of miR-550 was searched in miRBase database. Target genes of miR-550a-5p were predicted by Microcosm,Miranda and Targetscan, and the predective results were collected, then the enrichment analyses of target gene function(GO) and signalling pathway(pathway of miR-550a-5p) were carried out by using gene ontology darabase and KEGG database.

RESULTS: The expression of miR-550a-5p in bone marrow of all MDS patients was higher than that in controls: the expression level of miR-550a-5p in low risk MDS and middl risk 1 MDS was 1.7 times of controls (P=1.23×10-10 ); the expression of miR-550a-5p in midde risk 2 MDS and high risk MDS was 1.9 times of controls (P=1.20×10-10 ); the expression of miR-550a-5p in tAML was 2.0 times of controls (P=5.61×10-10 ). The miR-550a-5p expression level was up-regulated gradually with the enhancement of disease risk of MDS, but there was no correlation between the expression level of miR-550a-5p and clinical pathologic characteristics of MDS(chromosome: Normal: 1.11±0.19, Abnormal:1.26±0.15, P>0.05; Percentage of Marrow Blasts: r=0.29,P=0.07; absolute neutrophil count: r=-0.02,P=0.89; hemoglobin level: r=0.09,P=0.57; platelet count: r=0.25,P=0.08). The sequence of miR-550 was conservative among different species, and the prediced results indicated that there were 19 target genes in intersection. The functions of target genes were enriched in regulation of stress-activated cascade, MAPK pathway, regulation of muscle organ development, regulation of protein homodimerization activity and other biological processes; they participated in some molecular functions including enzyme activity, combination processes of some molecules as protein, cAMP and domain existed in cell junction, synapse, coated vesicle, dendrite and other cellular components. Two of them-PDLIM2 and PSME1 were selected which might play a role in pathologic mechanism of MDS regulated by miR-550a-5p.

CONCLUSION: The expression of miR-550a-5p in bone marrow of MDS patients increases specifically, and miR-550a-5p may play a role in the pathogenesis of MDS through regulation of target genes, PDLIM2 and PSME1.