Polymorphisms in mirna binding sites may contribute to the pathobiology of aml : evidence based on in-silico analysis

Majid Gholizadeh,1 Mahsa tahmasebivand,2 Zahra bahmanpour,3 Mehdi allahbakhshian farsani,4,*

1. Department of hematology and blood banking ,faculty of allied medicine,shahid beheshti university of medical sciences,Tehran,Iran
2. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
4. Department of hematology and blood banking ,faculty of allied medicine,shahid beheshti university of medical sciences,Tehran,Iran

Abstract

Introduction

Micrornas (mirnas) are a class of small (∼22 nucleotide) non-coding rnas that have key role in the posttranscriptional regulation of gene expression. the crucial step in the process of mirna-mediated regulation of gene expression is recognition of the target transcript by mirna. polymorphisms in microrna-binding sites (mirsnps) in target genes may alter the strength of microrna interaction with target genes thereby affecting protein levels. mirsnps, have attracted increasing attention due to their possible involvement in the development of various types of hematologic malignancy including acute myeloid leukemia (aml). in this study, through in-silico analysis we introduce novel mirsnps involved in aml.

Methods

Review of the current literature, showed that nucleophosmin (nmp1) could be important gene in aml. following this, mirnas associated with npm1 was distinguish in gene expression omnibus (geo) database, and other validated mirnas were obtained from mirtarbase, and finally common mirnas among them identified by venn diagram. in the next step, snps resided in target site of mirnas were listed from polymirts database, and for more investigation of mirnas related to aml obtained from disease-related databases such as mircancer. the resulting mirna: mrna: snps were further evaluated for the functional evidence supporting their involvement in aml.

Results

In-silico analysis revealed that hsa-mir-15b, rs:75508733/ hsa-mir-25, rs:186933329/ hsa-mir-27a-3p, rs:202141313/ and hsa-mir-302c-3p, rs:99971565 may have a functional interaction pertaining to the aml pathogenesis

Conclusion

Results showed that rs:75508733, rs:186933329, rs:202141313, rs:99971565 may potentially disrupt a functional interaction between mir-15b, mir-27, mir-27a, mir-302c and npm1, leading to dysregulation of npm1, and these snps may potentially contribute to the pathogenesis of aml and can be considered as significant progressive and prognostic factors in aml. in this study, a number of novel mir-snps have been introduced which could be considered by researchers for experimentation and validation studies.

Keywords

Mirsnps, in silico, acute myeloid leukemia (aml)