In silico analysis of siglec14 as a target for hsa-let-7e-5p

Negar Noorbakhsh,1,* Hamid galehdari,2 Narjes khaton shabani sadr,3

Abstract

Introduction

Sialic acid-binding immunoglobulin-type lectins (siglecs) are transmembrane proteins that are expressed on the cell surface and bind to sialic acids. the human siglec family includes 14 members that are predominantly expressed by cells of the immune system. siglecs have an extracellular sialic acid binding domain and an intracellular signaling domain. siglecs have emerged as important immunomodulatory receptors that alter immune cell function on binding to sialic acids. this concept is further supported by recent studies showing that disturbances in the sialic acid–siglec axis contribute to autoimmunity, infection, inflammation, aging, and cancer. siglecs are expressed predominantly by immune cells and can be divided into two groups: the conserved siglecs (siglec-1, -2, -4, and -15) and the cd33-related siglecs (siglec-3, -5, -6, -7, -8, -9, -10, -11, -14, and -16). siglec14 express in the neutrophils and monocytes and granulocytes and suggested that triggers proinflammatory pathway in monocytes. mirnas are a class of approximately 22-nt noncoding rnas that regulate gene expression at the post-transcriptional level. they bind to the 3-utr of the target mrnas and lead to degradation or translational inhibition of the target. they regulate diverse developmental processes, molecular and cellular pathways and are associated with cancer and other human diseases. prediction and validation of mirna targets are essential for understanding functions of mirnas in gene regulation. in the recent years, several bioinformatic tools have been developed to manage the mounting flow of mirna-related data. a large number of bioinformatic tools are now available to manage the mounting data flow. it is well established that mirnas down-regulate gene expression by targeting 3utrs of mrnas through sequence-specific binding. knowing mirna targets is essential to understand their function. validating a possible mirna target in the laboratory is expensive and time-consuming, since each mirna has a large number of potential target sites. computational approaches help reduce their number for experimental validation. most applications are accessible through an online interface.

Methods

Identification of gene targets is critical for characterizing the functions of mirnas and in this project the effect of the hsa-let-7e-5p on siglec 14 was investigated. by using bioinformatics algorithms such as targetscan, mirdb, diana and starmir, the sites in mrnas of siglec 14 which can react with hsa-let-7e-5p, were predicted.

Results

In this study, our results showed that siglec14 is a target of the hsa-let-7e-5p. to make our predicted target gene more convinced, four common target gene databases selected. length of 3’-utr siglec14 according to mirdb is 802bp. Δg hybrid interactive of siglec14 and hsa-let-7e-5p in 3'-utr seed region in starmir for 8mer seed type is -19.500.

Conclusion

Therapeutic strategies can be designed to target mirnas that affect common pathways, thereby enabling modulation of mrna levels to increase cell survival, reduce inflammation, and promote cell proliferation and differentiation in the various injuries.

Keywords

Mirna, siglec14, hsa-let-7e-5p