Expression significance and potential mechanism of hypoxia-inducible factor 1 alpha in patients with myelodysplastic syndromes.

ABSTRACT: OBJECTIVE:To investigate the expression level and potential mechanism of hypoxia-inducible factor 1 alpha (HIF-1?) in patients with myelodysplastic syndromes (MDS). METHODS:Immunohistochemistry (IHC) techniques were used to examine the protein expression of HIF-1? in paraffin-embedded myeloid tissues from 82 patients with MDS and 33 controls (patients with lymphoma that is not invading myeloid tissues). In addition, the associations between the protein expression of HIF-1? and clinical parameters were examined. To further investigate the significance of HIF-1? expression in MDS patients, the researchers not only extracted the data about HIF-1? expression from MDS-related microarrays but also analyzed the correlation between the level of HIF-1? expression and MDS. The microRNA (miRNA) targeting HIF-1? was predicted and verified with a dual luciferase experiment. RESULTS:Immunohistochemistry revealed that the positive expression rate of HIF-1? in the bone marrow of patients with MDS was 90.24%. This rate was remarkably higher than that of the controls (72.73%) and was statistically significant (P < .05), which indicated that HIF-1? was upregulated in the myeloid tissues of MDS patients. For the GSE2779, GSE18366, GSE41130, and GSE61853 microarrays, the average expression of HIF-1? in MDS patients was higher than in the controls. Particularly for the GSE18366 microarray, HIF-1? expression was considerably higher in MDS patients than in the controls (P < .05). It was predicted that miR-93-5p had a site for binding with HIF-1?, and a dual luciferase experiment confirmed that miR-93-5p could bind with HIF-1?. CONCLUSION:The upregulated expression of HIF-1? was examined in the myeloid tissues of MDS patients. The presence of HIF-1? (+) suggested an unsatisfactory prognosis for patients, which could assist in the diagnosis of MDS. In addition, miR-93-5p could bind to HIF-1? by targeting, showing its potential to be the target of HIF-1? in MDS.

SUBMITTER: Liang HW 

PROVIDER: S-EPMC6792495 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature