Transcriptomics

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Cytoplasmic Miz1 Suppresses TNF-α-Induced NF-κB Activation and Hepatocellular Carcinoma Progression via the Interaction with Metadherin


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE104940 | GEO | 2020/10/11

REPOSITORIES: GEO

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