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Series GSE77323 Query DataSets for GSE77323
Status Public on Nov 23, 2016
Title p62, upregulated during preneoplasia, induces hepatocellular carcinogenesis by maintaining survival of stressed HCC-initiating cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary p62/SQSTM1 is a ubiquitin-binding autophagy receptor and signaling protein that accumulates in premalignant liver diseases and most hepatocellular carcinomas (HCC). Although p62 was proposed to participate in formation of benign adenomas in autophagy-deficient livers, its role in HCC initiation was not explored. Here we show that p62 is necessary and sufficient for HCC induction in mice and that its high expression level in non-tumor human liver predicts rapid HCC recurrence after curative ablation. High p62 expression is needed for activation of NRF2 and mTORC1, c-Myc induction and protection of HCC-initiating cells from oxidative stress-induced death.
Overall design p62F/F and Tsc1 F/F mice (Mori et al., 2009; Muller et al., 2013) were backcrossed to C57BL/6 mice for at least 7 generations, and then bred with Alb-Cre transgenic mice (also on C57BL/6 background) to generate p62F/F; Alb-Cre (p62Δhep) and Tsc1F/F; Alb-Cre (Tsc1Δhep)mice, respectively. p62Δhep mice were crossed to Tsc1Δhep and MUP-uPA mice to generate p62F/F; Tsc1F/F; Alb-Cre (Tsc1/p62Δhep) mice and p62Δhep/MUP-uPA transgenic mice, respectively. Genotyping was performed as described (Muller et al., 2013). All animal studies were in accordance with NIH guidelines for use and care of live animals and were approved by the UCSD Institutional Animal Care and Use Committee. Mice were maintained in filter-topped cages on autoclaved chow diet (low-fat diet; LFD, composed of 12% fat, 23% protein, 65% carbohydrates based on caloric content) or high-fat diet (HFD, composed of 59% fat, 15% protein, 26% carbohydrates based on caloric content; Bio-Serv) and water at UCSD according to NIH Guidelines.
Contributor(s) Umemura A, He F, Nakagawa H, Yamachika S, Taniguchi K, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M
Citation(s) 27211490
Submission date Jan 28, 2016
Last update date Jul 07, 2022
Contact name Jorge Moscat
Department Pathology and Laboratory Medicine
Lab Moscat and Diaz-Meco
Street address 1188 York Avenue
City New York
State/province NY
ZIP/Postal code 10065
Country USA
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (12)
GSM2049237 p62f/f mice Cre negative - WT 1
GSM2049238 p62f/f mice Cre negative - WT 2
GSM2049239 p62f/f mice Cre negative - WT 3
BioProject PRJNA310105
SRA SRP069010

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Supplementary file Size Download File type/resource
GSE77323_DKO_vs_TSC1KONORMAL.deseq.counts.csv.gz 264.1 Kb (ftp)(http) CSV
GSE77323_p62f_vs_p62fAlbCre.deseq.counts.csv.gz 261.8 Kb (ftp)(http) CSV
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Processed data are available on Series record
Raw data are available in SRA

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