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‐1α) in patients with myelodysplastic syndromes (MDS). Methods Immunohistochemistry (IHC) techniques were used to examine the protein expression of HIF‐1α 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‐1α and clinical parameters were examined. To further investigate the significance of HIF‐1α expression in MDS patients, the researchers not only extracted the data about HIF‐1α expression from MDS‐related microarrays but also analyzed the correlation between the level of HIF‐1α expression and MDS. The microRNA (miRNA) targeting HIF‐1α was predicted and verified with a dual luciferase experiment. Results Immunohistochemistry revealed that the positive expression rate of HIF‐1α 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‐1α was upregulated in the myeloid tissues of MDS patients. For the GSE2779, GSE18366, GSE41130, and GSE61853 microarrays, the average expression of HIF‐1α in MDS patients was higher than in the controls. Particularly for the GSE18366 microarray, HIF‐1α 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‐1α, and a dual luciferase experiment confirmed that miR‐93‐5p could bind with HIF‐1α. Conclusion The upregulated expression of HIF‐1α was examined in the myeloid tissues of MDS patients. The presence of HIF‐1α (+) suggested an unsatisfactory prognosis for patients, which could assist in the diagnosis of MDS. In addition, miR‐93‐5p could bind to HIF‐1α by targeting, showing its potential to be the target of HIF‐1α in MDS.

Global Proteomics Analysis of Bone Marrow: Establishing Talin-1 and Centrosomal Protein of 55 kDa as Potential Molecular Signatures for Myelodysplastic Syndromes

“…Several genes that define normal blood cells are regulated by miRNAs, and MDS prognosis is linked to certain miRNAs of the bone marrow, peripheral blood, and mononuclear cells ( 69 ). In fact, some CEP55 -controlling miRNAs identified in our in silico model have been listed as differentially expressed in other patients with MDS ( 70 , 71 , 81 , 82 ).…”

Long-term proliferation of immature hypoxia-dependent JMML cells supported by a 3D in vitro system

“…Our data show that proliferation of immature JMML cells is mainly due to hypoxic conditions, suggesting that low oxygen tension is an essential feature for the preservation of the leukemic cell status. It has been demonstrated that HIF-1α expression and its stabilization into nuclei is peculiar of stem cells in MDS, supporting leukemia cell proliferation and self-renewal [44] and that this could represent a promising therapeutic target [45][46][47].…”

Identification of MiR-93-5p Targeted Pathogenic Markers in Acute Myeloid Leukemia through Integrative Bioinformatics Analysis and Clinical Validation

“…Unfortunately, we have not yet found research reports on the exact mechanism of the specific regulatory relationship between miR-93-5p and VEGF . However, after predicting target genes through the TargetScan Human database ( http://www.targetscan.org ), we discovered that miRNA-93 might be targeting hypoxia-inducible factor 1 α ( HIF-1α ) affecting the expression of VEGF [ 61 ]. At the same time, studies have found that the miRNA-93 consensus sequence also exists in the 3′UTR region of VEGF mRNA, which inspires our next research: miRNA-93 may mediate the occurrence development of AML by regulating the expression of HIF-1α/VEGF [ 22 ].…”