Pbrm1 Loss Induces a Permissive Chromatin State for Cholangiocytic Differentiation and Cholangiocarcinoma Formation

Cellular and Molecular Gastroenterology and Hepatology 2026 Open access

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Authors: Li-Wen Chiou, Yu-Lin Jhuang, Chia-Lang Hsu, Ray‐Hwang Yuan, Yen-Hsu Cheng, Chia-Hsiang Lee, Yi-Ting Fang, Ching-Yao Yang, Jeng Yung-Ming
DOI: 10.1016/j.jcmgh.2025.101720
Cited by: 3
References: 47

Abstract

BACKGROUND & AIMS: The SWI/SNF ATP-dependent chromatin remodeling complex regulates transcriptional machinery access and is critical in normal physiology and cancer development. PBRM1, a key subunit of this complex, is frequently mutated in intrahepatic cholangiocarcinoma (iCCA). This study aims to explore the role of PBRM1 in liver physiology and its involvement in iCCA development. METHODS: mutation to study cancer development. RESULTS: mice predominantly developed hepatocellular neoplasms. PBRM1-deficient organoids were highly sensitive to the EZH2 inhibitor tazemetostat, whereas effects on allografts were limited. CONCLUSIONS: PBRM1 maintains chromatin accessibility for hepatocyte differentiation-related genes. Its loss promotes differentiation toward cholangiocytes during injury or tumorigenesis, driving iCCA development.

Fields of Study & Subjects

Cholangiocarcinoma and Gallbladder Cancer Studies Liver physiology and pathology Chromatin Remodeling and Cancer

Publication details

Journal / source
Cellular and Molecular Gastroenterology and Hepatology
Publisher
Elsevier BV
Volume
20
Issue
6
Pages
101720–101720
Publication date
1 January 2026
Language
EN