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Series GSE104940 Query DataSets for GSE104940
Status Public on Oct 11, 2020
Title Cytoplasmic Miz1 Suppresses TNF-α-Induced NF-κB Activation and Hepatocellular Carcinoma Progression via the Interaction with Metadherin
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Previous studies have revealed that nuclear Miz1 is implicated in the regulation of several cancers mainly relying on its POZ domain. Current study, however, uncovers an unexpected function of cytoplasmic Miz1 in hepatocellular carcinoma (HCC). In vivo HCC models in Miz1 and Miz1(POZ) KO mice along with RNA-sequencing experiments show that hepatocyte specific ablation of Miz1 exacerbates TNF-α-induced NF-κB activation and promotes the progression of HCC independent of its transcriptional activity. Ubiquitination and proteosomal degradation of cytoplasmic Miz1 liberates its novel partner Metadherin (MTDH), and its site specific phosphorylation is critical to NF-κB activation. These findings reveal a brand new role of cytosolic Miz1 as a suppressor of HCC, and provide profound insights into liver cancer diagnosis and treatment.
Overall design Miz1fl/fl and Miz1(POZ)fl/fl mice were crossed with Alb-Cre transgenic mice (C57BL/6 background) to generate an hepatocyte specific knock out of Miz1 and Miz1(POZ) respectively(Miz1△Hep, Miz1(POZ)△Hep). For different groups of mice (Miz1fl/fl, Miz1△Hep, Miz1(POZ)fl/fl, Miz1(POZ)△Hep), HCC was induced by the combination of DEN (25 mg/kg i.p.) given at Week 2 postpartum followed by weekly injections of CCl4 (0.5 ml/kg i.p., dissolved in corn oil). Mice were sacrificed at the age of 5 months and pure tumors from Miz1fl/fl, Miz1△Hep, Miz1(POZ)fl/fl, Miz1(POZ)△Hep mice were subjected to RNA sequencing, in triplicate. All animal experimental protocols were approved by the Animal Ethics Committee of Nanjing Medical University.
Contributor(s) Zhang W, Zhangyuan G, Jin K, Wang F, Wang X, Yu W, Huang R, Xu X, Shen H, Du M, Zhang H, Yin Y, Zhong G, Lin A, Sun B
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Submission date Oct 13, 2017
Last update date Oct 11, 2020
Contact name Guangyan Zhangyuan
Phone 86-025-86560946
Organization name Nanjing University
Department Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School
Street address 321 Zhongshan Road
City Nanjing
State/province Jiangsu
ZIP/Postal code 210000
Country China
Platforms (2)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (12)
GSM2810336 Miz1fl/fl AlbCre negative 1
GSM2810337 Miz1fl/fl AlbCre negative 2
GSM2810338 Miz1fl/fl AlbCre negative 3
BioProject PRJNA414205
SRA SRP119908

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Supplementary file Size Download File type/resource
GSE104940_Miz1.xls.gz 1.3 Mb (ftp)(http) XLS
GSE104940_Miz1_POZ_.xls.gz 843.9 Kb (ftp)(http) XLS
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Processed data are available on Series record

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