RNA-seq analysis reveals transcriptome changes in livers from Efcab4b knockout mice

EFCAB4B is an evolutionarily conserved protein that encodes for the Rab GTPase Rab46, and the CRAC channel modulator, CRACR2A. Previous genome wide association studies have demonstrated the association of EFCAB4B variants in the progression of non-alcoholic fatty liver disease (NAFLD). In this study...

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Main Authors: Chew W. Cheng, Lucia Pedicini, Cintli Morales Alcala, Fenia Deligianni, Jessica Smith, Ryan D. Murray, Harriet J. Todd, Niamh Forde, Lynn McKeown
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Biochemistry and Biophysics Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405580825000317
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author Chew W. Cheng
Lucia Pedicini
Cintli Morales Alcala
Fenia Deligianni
Jessica Smith
Ryan D. Murray
Harriet J. Todd
Niamh Forde
Lynn McKeown
author_facet Chew W. Cheng
Lucia Pedicini
Cintli Morales Alcala
Fenia Deligianni
Jessica Smith
Ryan D. Murray
Harriet J. Todd
Niamh Forde
Lynn McKeown
author_sort Chew W. Cheng
collection DOAJ
description EFCAB4B is an evolutionarily conserved protein that encodes for the Rab GTPase Rab46, and the CRAC channel modulator, CRACR2A. Previous genome wide association studies have demonstrated the association of EFCAB4B variants in the progression of non-alcoholic fatty liver disease (NAFLD). In this study we show that mice with global depletion of Efcab4b−/− have significantly larger livers than their wild-type (WT) counterparts. We performed RNA-sequencing (RNA-seq) analysis of liver tissues to investigate differential global gene expression among Efcab4b−/− and WT mice. Of the 69 differentially expressed genes (DEGs), analyses of biological processes found significant enrichment in liver and bile development, with 6 genes (Pck1, Aacs, Onecut1, E2f8, Xbp1, and Hes1) involved in both processes. Specific consideration of possible roles of DEGs or their products in NAFLD progression to (NASH) and hepatocarcinoma (HCC), demonstrated DEGs in the livers of Efcab4b−/− mice had roles in molecular pathways including lipid metabolism, inflammation, ER stress and fibrosis. The results in this study provide additional insights into molecular mechanisms responsible for increasing susceptibility of liver injuries associated with EFCAB4B.
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spelling doaj-art-46dee9106da14f419e255f80d0163d212025-08-20T02:46:29ZengElsevierBiochemistry and Biophysics Reports2405-58082025-03-014110194410.1016/j.bbrep.2025.101944RNA-seq analysis reveals transcriptome changes in livers from Efcab4b knockout miceChew W. Cheng0Lucia Pedicini1Cintli Morales Alcala2Fenia Deligianni3Jessica Smith4Ryan D. Murray5Harriet J. Todd6Niamh Forde7Lynn McKeown8University of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UKUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UKUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UKUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UKUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UKUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UKUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UKUniversity of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UKCorresponding author.; University of Leeds, Faculty of Medicine and Health, Leeds Institute of Cardiovascular and Metabolic Medicine, Leeds, LS2 9JT, UKEFCAB4B is an evolutionarily conserved protein that encodes for the Rab GTPase Rab46, and the CRAC channel modulator, CRACR2A. Previous genome wide association studies have demonstrated the association of EFCAB4B variants in the progression of non-alcoholic fatty liver disease (NAFLD). In this study we show that mice with global depletion of Efcab4b−/− have significantly larger livers than their wild-type (WT) counterparts. We performed RNA-sequencing (RNA-seq) analysis of liver tissues to investigate differential global gene expression among Efcab4b−/− and WT mice. Of the 69 differentially expressed genes (DEGs), analyses of biological processes found significant enrichment in liver and bile development, with 6 genes (Pck1, Aacs, Onecut1, E2f8, Xbp1, and Hes1) involved in both processes. Specific consideration of possible roles of DEGs or their products in NAFLD progression to (NASH) and hepatocarcinoma (HCC), demonstrated DEGs in the livers of Efcab4b−/− mice had roles in molecular pathways including lipid metabolism, inflammation, ER stress and fibrosis. The results in this study provide additional insights into molecular mechanisms responsible for increasing susceptibility of liver injuries associated with EFCAB4B.http://www.sciencedirect.com/science/article/pii/S2405580825000317Human EFCAB4B (Rab46 / CRACR2A)Mouse Efcab4bLiverNon-alcoholic steatohepatitis (NASH)Hepatocarcinoma (HCC)Non-alcoholic fatty liver disease (NAFLD)
spellingShingle Chew W. Cheng
Lucia Pedicini
Cintli Morales Alcala
Fenia Deligianni
Jessica Smith
Ryan D. Murray
Harriet J. Todd
Niamh Forde
Lynn McKeown
RNA-seq analysis reveals transcriptome changes in livers from Efcab4b knockout mice
Biochemistry and Biophysics Reports
Human EFCAB4B (Rab46 / CRACR2A)
Mouse Efcab4b
Liver
Non-alcoholic steatohepatitis (NASH)
Hepatocarcinoma (HCC)
Non-alcoholic fatty liver disease (NAFLD)
title RNA-seq analysis reveals transcriptome changes in livers from Efcab4b knockout mice
title_full RNA-seq analysis reveals transcriptome changes in livers from Efcab4b knockout mice
title_fullStr RNA-seq analysis reveals transcriptome changes in livers from Efcab4b knockout mice
title_full_unstemmed RNA-seq analysis reveals transcriptome changes in livers from Efcab4b knockout mice
title_short RNA-seq analysis reveals transcriptome changes in livers from Efcab4b knockout mice
title_sort rna seq analysis reveals transcriptome changes in livers from efcab4b knockout mice
topic Human EFCAB4B (Rab46 / CRACR2A)
Mouse Efcab4b
Liver
Non-alcoholic steatohepatitis (NASH)
Hepatocarcinoma (HCC)
Non-alcoholic fatty liver disease (NAFLD)
url http://www.sciencedirect.com/science/article/pii/S2405580825000317
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