TRIM24 suppresses development of spontaneous hepatic lipid accumulation and hepatocellular carcinoma in mice

Shiming Jiang, Lindsey Cauthen Minter, Sabrina A. Stratton, Peirong Yang, Hussein A. Abbas, Zeynep Coban Akdemir, Vinod Pant, Sean Post, Mihai Gagea, Richard G. Lee, Guillermina Lozano, Michelle Craig Barton

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Background & Aims: Aberrantly high expression of TRIM24 occurs in human cancers, including hepatocellular carcinoma. In contrast, TRIM24 in the mouse is reportedly a liver-specific tumour suppressor. To address this dichotomy and to uncover direct regulatory functions of TRIM24 in vivo, we developed a new mouse model that lacks expression of all Trim24 isoforms, as the previous model expressed normal levels of Trim24 lacking only exon 4. Methods: To produce germline-deleted Trim24dlE1 mice, deletion of the promoter and exon 1 of Trim24 was induced in Trim24LoxP mice by crossing with a zona pellucida 3-Cre line for global deletion. Liver-specific deletion (Trim24hep) was achieved by crossing with an albumin-Cre line. Phenotypic analyses were complemented by protein, gene-specific and global RNA expression analyses and quantitative chromatin immunoprecipitation. Results: Global loss of Trim24 disrupted hepatic homeostasis in 100% of mice with highly significant, decreased expression of oxidation/reduction, steroid, fatty acid, and lipid metabolism genes, as well as increased expression of genes involved in unfolded protein response, endoplasmic reticulum stress and cell cycle pathways. Trim24dlE1/dlE1 mice have markedly depleted visceral fat and, like Trim24hep/hep mice, spontaneously develop hepatic lipid-filled lesions, steatosis, hepatic injury, fibrosis and hepatocellular carcinoma. Conclusions: TRIM24, an epigenetic co-regulator of transcription, directly and indirectly represses hepatic lipid accumulation, inflammation, fibrosis and damage in the murine liver. Complete loss of Trim24 offers a model of human non-alcoholic fatty liver disease, steatosis, fibrosis and development of hepatocellular carcinoma in the absence of high-fat diet or obesity.

Original languageEnglish (US)
Pages (from-to)371-379
Number of pages9
JournalJournal of Hepatology
Issue number2
StatePublished - 2015
Externally publishedYes


  • HCC
  • Hepatic lesions
  • Histone reader
  • NASH
  • Steatosis

ASJC Scopus subject areas

  • Hepatology


Dive into the research topics of 'TRIM24 suppresses development of spontaneous hepatic lipid accumulation and hepatocellular carcinoma in mice'. Together they form a unique fingerprint.

Cite this