Regulation of the Lewis Blood Group Antigen Expression: A Literature Review Supplemented with Computational Analysis

Abstract

<b><i>Background:</i></b> The Lewis (Le) blood group system, unlike most other blood groups, is not defined by antigens produced internally to the erythrocytes and their precursors but rather by glycan antigens adsorbed on to the erythrocyte membrane from the plasma. These oligosaccharides are synthesized by the two fucosyltransferases <i>FUT2</i> and <i>FUT3</i> mainly in epithelial cells of the digestive tract and transferred to the plasma. At their place of synthesis, some Lewis blood group carbohydrate antigen variants also seem to be involved in various gastrointestinal malignancies. However, relatively little is known about the transcriptional regulation of <i>FUT2</i> and <i>FUT3</i>. <b><i>Summary:</i></b> To address this question, we screened existing literature and additionally used in silico prediction tools to identify novel candidate regulators for <i>FUT2</i> and <i>FUT3</i> and combine these findings with already known data on their regulation. With this approach, we were able to describe a variety of transcription factors, RNA binding proteins and microRNAs, which increase <i>FUT2</i> and <i>FUT3</i> transcription and translation upon interaction. <b><i>Key Messages:</i></b> Understanding the regulation of <i>FUT2</i> and <i>FUT3</i> is crucial to fully understand the blood group system Lewis (ISBT 007 LE) phenotypes, to shed light on the role of the different Lewis antigens in various pathologies, and to identify potential new diagnostic targets for these diseases.