Tumor suppressive role of the antimicrobial lectin REG3A targeting the O-GlcNAc glycosylation pathway

Sep 21, 2026

Antimicrobial proteins of the regenerating family member 3 alpha (REG3A) provide a first line of protection against infections and transformed cells, with expression inducible by inflammation, complicating their cancer relevance. This study clarifies REG3A’s role in liver carcinogenesis and tests whether its carbohydrate-binding functions participate. Results show REG3A suppresses HCC by reducing O-GlcNAcylation, decreasing UDP-GlcNAc, and improving cancer-free survival in high-REG3A cirrhotic patients.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Background and Aims

Approach and Results

Conclusions

Introduction

C-type lectins and pattern recognition receptors

DOI: 10.1097/HEP.0000000000000993 O R IG INAL ART ICL E Tumor suppressive role of the antimicrobial lectin REG3A targeting the O-GlcNAc glycosylation pathway Nicolas Moniaux1,2 | Nicolas Geoffre1,2 | Alice Deshayes1,2 | Alexandre Dos Santos1,2 | Sylvie Job1,2 | Claire Lacoste1,2 | Tung-Son Nguyen1,2 | Marion Darnaud1,2 | Mélanie Friedel-Arboleas3 | Catherine Guettier1,2,4 | Janne Purhonen5,6 | Jukka Kallijärvi5,6 | Gilles Amouyal7 | Paul Amouyal7 | Christian Bréchot8 | Romain R. Vivès3 | Marie Annick Buendia1,2 | Tarik Issad9 | Jamila Faivre1,2,10 1INSERM, U1193, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif, France 2Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France 3 Université Grenoble Alpes, CNRS, CEA, IBS, Grenoble, France 4Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Saclay, Hôpital Bicêtre, Laboratoire Anatomie Pathologique, Le Kremlin Bicêtre, France 5Folkhälsan Research Center, Helsinki, Finland 6Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland 7Alfact Innovation, Paris, France 8USF Health, University of South Florida, Tampa, Florida, USA 9Institut Cochin, Université de Paris, CNRS, INSERM, Paris, France 10Assistance Publique-Hôpitaux de Paris (AP-HP), Medical-University Department (DMU) Biology Genetics, Université Paris-Saclay, Paul-Brousse Hospital, Villejuif, France Correspondence Nicolas Moniaux, U1193 INSERM (French National Institute of Health and Medical Research)/University Paris-Saclay, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif 94800, France. Email: [nicolas.moniaux@inserm.fr](nicolas.moniaux@inserm.fr) Jamila Faivre, U1193 INSERM/University Paris-Saclay, Paul-Brousse University Hospital, Hepatobiliary Centre, Villejuif 94800, France. Email: [jamila.faivre@inserm.fr](jamila.faivre@inserm.fr) | | Abstract | | | --- | --- | --- | | | Background and Aims: Antimicrobial proteins of the regenerating | | | | family member 3 alpha (REG3A) family provide a first line of protection | | | | against infections and transformed cells. Their expression is inducible by | | | | inflammation, which makes their role in cancer biology less clear since an | | | | immune-inflammatory context may preexist or coexist with cancer, as occurs | | | | in HCC. The aim of this study is to clarify the role of REG3A in liver | | | | carcinogenesis and to determine whether its carbohydrate-binding functions are involved. | | | | | | Abbreviations: CRB, Centre de Ressources Biologiques (biological resource center); DEN, diethylnitrosamine; EXTL3, exostosin-like glycosyltransferase 3; Fru, fructose; Fru-6P, fructose-6 phosphate; Gal, galactose; GFAT, glutamine fructose-6-phosphate amidotransferase; Glc, glucose; Glc-1P, glucose-1 phosphate; Glc-6P, glucose-6 phosphate; GlcNac, N-acetyl glucosamine; GlcNac-6P, N-acetyl glucosamine 6 phosphate; gp130, glycoprotein 130; HBP, hexosamine biosynthetic pathway; NT, nontumor; O-GlcNAc, O-linked N-acetylglucosamine; OGA, O-linked N-acetylglucosaminyl hydrolase; OGT, O-linked N-acetylglucosaminyltransferase; REG3A, regenerating family member 3 alpha; T, tumor; UDP, uridine diphosphate; WT, wild-type. Nicolas Moniaux and Jamila Faivre contributed equally to this work. Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal’s website, [www.hepjournal.com](www.hepjournal.com). -- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- - This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without per

FAQs

What is the main aim of the study on REG3A?

The study aims to clarify REG3A’s role in liver carcinogenesis and determine whether its carbohydrate-binding functions are involved.

How does REG3A influence O-GlcNAcylation and HCC development?

REG3A suppresses HCC by reducing global O-GlcNAcylation in pre-neoplastic and tumor livers. This effect is linked to decreased UDP-GlcNAc levels and the ability of REG3A to bind glucose and glucose-6 phosphate.

Does changing REG3A affect key enzymes in the O-GlcNAc pathway?

The study reports that REG3A modified O-GlcNAcylation without altering the expression or activity of OGT, OGA, or GFAT-related components tested.

Sep 21, 2026

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