The importance of MIR-4328 gene mutations in Acute Promyelocytic Leukemia

Introduction: miRNAs are involved in the pathogenesis of neoplastic syndromes by silencing target genes. As previously shown, hsa-mir-4328 is downregulated in Acute Promyelocytic Leukemia (APL). Objectives: The study aims to identify the somatic mutations of the MIR-4328 gene that caused its downregulation in APL and their localization in key regions of the mature miRNA structure. Material and methods: The study included 24 subiects: the study group (10 patients at the onset of APL, as well as at remission and relapse) and the control group (10 apparently healthy patients). High-Resolution Melting (HRM) was used for genotyping. Results: As MIR-4328 gene has not been studied before, a structure design of the coding region was performed to better understand the impact of somatic mutations on the mature miRNA. Following HRM, 2 mutant genotypes were identified, different from the wild-type (WT) genes. Conclusions and discussion: Due to the major deviation of the mutant genotypic curves compared to WT, the existence of major mutations (probably insertions/deletions) can be assumed. If these mutations are located in the seed region of the gene, attachment to exon 3 of the RARA gene is no longer possible, and therefore overexpression of the target gene occurs. Also, frameshift mutations, or substitutions that change the nucleotide sequence of the seed region, can produce a completely different mature miRNA that may have tropism for another gene. To test these hypotheses, sequencing of the entire gene is required.