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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 05, 2020 |
| Title |
Comparative gene expression profiling in livers of A1cf-transgenic and wild-type mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Rationale: RNA binding protein Apobec1 Complementation Factor (A1CF) regulates posttranscriptional ApoB mRNA editing but the range of RNA targets and long-term impact of altered A1CF expression on liver function are unknown. Objective: We studied hepatocyte-specific A1cf transgenic (A1cf +/Tg), A1cf+/Tg Apobec1– /– and A1cf –/– mice fed chow or high fat/high fructose diets using RNA-Seq, RNA-CLIP Seq and tissue microarrays from human hepatocellular cancer (HCC). Findings: A1cf +/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution. Aged A1cf +/Tg mice developed spontaneous fibrosis, dysplasia and HCC, which was accelerated on a high fat/fructose diet and independent of Apobec1. RNA-Seq revealed increased expression of mRNAs involved in oxidative stress (Gstm3, Gpx3, Cbr3), inflammatory response (Il19, Cxcl14, Tnfα, Ly6c), extracellular matrix organization (Mmp2, Col1a1, Col4a1), proliferation (Kif20a, Mcm2, Mcm4, Mcm6) with a subset of mRNAs (including Sox4, Sox9, Cdh1) identified in RNA CLIP-Seq. Increased A1CF expression in human HCC correlated with advanced fibrosis and with reduced survival in a subset with nonalcoholic fatty liver disease. Conclusions: Hepatic A1CF overexpression selectively alters polysomal distribution and mRNA expression, promoting lipogenic, proliferative and inflammatory pathways leading to HCC.
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| Overall design |
Samples from A1cf-transgenic mice were compared to samples from age-matched wild-type C57BL/6NJ mice as a reference. For each genotype, pools were prepared containing RNAs from 3-4 separate mice, labeled, and hybridized to Agilent microarrays.
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| Contributor(s) |
Blanc V, Riordan JD, Soleymanjahi S, Nadeau JH, Nalbantoglu I, Xie Y, Molitor EA, Madison BB, Brunt EM, Mills JC, Rubin DC, Ng IO, Ha Y, Roberts LR, Davidson NO |
| Citation(s) |
33445170 |
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| Submission date |
Sep 04, 2020 |
| Last update date |
Jan 18, 2021 |
| Contact name |
Jesse Riordan |
| E-mail(s) |
jesse-riordan@uiowa.edu
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| Organization name |
University of Iowa
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| Street address |
375 Newton Road
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| City |
Iowa City |
| State/province |
IA |
| ZIP/Postal code |
52240 |
| Country |
USA |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA661555 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE157516_RAW.tar |
13.1 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
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