RRC ID 65471
Author Tian H, Ge C, Zhao F, Zhu M, Zhang L, Huo Q, Li H, Chen T, Xie H, Cui Y, Yao M, Li J.
Title Downregulation of AZGP1 by Ikaros and histone deacetylase promotes tumor progression through the PTEN/Akt and CD44s pathways in hepatocellular carcinoma.
Journal Carcinogenesis
Abstract Increasing evidence has shown that zinc-alpha2-glycoprotein (AZGP1) is associated with the progression and prognosis of several tumor types. However, little is known regarding the underlying molecular mechanisms of AZGP1 in hepatocellular carcinoma (HCC). In this study, we report that transcription factor Ikaros bound to the AZGP1 promoter and increased its expression in HCC cells. The downregulation of AZGP1 was associated with histone deacetylation in HCC. In addition, the positive feedback regulation via acetylation of histone H4-mediated transactivation of the Ikaros promoter and the Ikaros-mediated transactivation of the acetylation of histone H4 were crucial for regulating AZGP1 expression in HCC cells. Moreover, low serum AZGP1 level in HCC patients was associated with poor prognosis. The ectopic overexpression of AZGP1 or recombinant AZGP1 protein inhibited HCC cell proliferation, migration and invasion in vitro and in vivo, whereas silencing AZGP1 expression resulted in increased cell proliferation, migration and invasion in vitro. In addition, we found that AZGP1 inhibited cell migration and invasion through the regulation of the PTEN/Akt and CD44s pathways. Collectively, our findings revealed the molecular mechanism of AZGP1 expression in HCC, providing new insights into the mechanisms underlying tumor progression.
Volume 38(2)
Pages 207-217
Published 2017-2-1
DOI 10.1093/carcin/bgw125
PII bgw125
PMID 27993894
MeSH Adipokines Animals Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / pathology Carrier Proteins / biosynthesis* Carrier Proteins / genetics Cell Movement / genetics Cell Proliferation / genetics Epithelial-Mesenchymal Transition / genetics* Gene Expression Regulation, Neoplastic Glycoproteins / biosynthesis* Glycoproteins / genetics Histone Deacetylases / genetics Humans Hyaluronan Receptors / genetics Ikaros Transcription Factor / genetics Liver Neoplasms / genetics* Liver Neoplasms / pathology Mice Oncogene Protein v-akt / genetics PTEN Phosphohydrolase / genetics Signal Transduction Xenograft Model Antitumor Assays
Human and Animal Cells Huh7