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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Elsevier
2025-03-01
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| 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. |
| format | Article |
| id | doaj-art-46dee9106da14f419e255f80d0163d21 |
| institution | DOAJ |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| 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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