Downregulation of hsa-miR-4328 and target gene prediction in Acute Promyelocytic Leukemia

Introduction: Acute promyelocytic leukemia (APL) is defined by the PML-RARA fusion gene. APL treatment can have significant side effects, therefore the development of optimal therapeutic options is crucial. Although the study of miRNAs is still in its infancy, it has been shown that these molecules are involved in the pathogenesis of neoplasms by modulating the expression of target genes. miRNAs can be considered possible biomarkers in APL and can be used as therapeutic targets or as markers for the therapeutic response. Objectives: The purpose of this study was to determine whether differentially expressed putative miRNAs that have RARA as a target gene could be considered reliable biomarkers for APL. Methods: Using bioinformatics tools, a panel of 6 miRNAs with possible tropism for the RARA gene was selected from miRDB. We evaluated their expression levels in samples from patients with APL (n=20) or from healthy subjects without mutations in genes associated with leukemia or myeloproliferative diseases (n=21). Results: All 6 putative miRNAs were identified using electrophoresis (hsamir-4299, hsa-mir-4328, hsa-mir-7851-3p, hsa-mir-6827-5p, hsa-mir-6867-5p, hsa-mir-939-5p). Of the six miRNAs, hsa-mir-4328 is deeply downregulated in subjects diagnosed with APL compared to healthy subjects, whereas hsa-mir-4299 and hsa-mir-7851-3p show small differences in expression between the two study groups, but without statistical significance. Our results suggest that hsa-mir-4328 may have a role in the pathogenesis of APL and may represent a new biomarker for this type of leukemia. Key Words: miRNA, APL, leukemia, bioinformatics.