Abstract
BackgroundKruppel family member zinc binding protein 89 (ZBP-89), also known as ZNF148, regulates Bak expression via binding to GC-rich promoter domain. It is not clear if other GC-rich binding factors, such as Sp family members, can interact with ZBPp-89 on Bak expression. This study aims to elucidate the mechanism of Bak expression regulation by ZBP-89 and Sp proteins, based on in vitro experiment and The Cancer Genome Atlas (TCGA) hepatocellular carcinoma (HCC) data cohort.MethodsWe downloaded TCGA hepatocellular carcinoma (HCC) cohort data to analysis the association of Bak transcription level with ZBP-89 and Sp proteins transcription level. HCC cell lines and liver immortal non-tumour cell lines were used for mechanism study, including western blotting analysis, expression vector mediated gene expression and siRNA interference.ResultsResults showed that cancer tissues have higher Bak transcription level compared with adjacent non-cancer tissues. Bak transcription level was correlated with Sp1 and Sp3 expression level, while no correlation was found in ZBP-89 and Bak, neither Sp2 nor Sp4. Mithramycin A (MMA) induced Bak expression in a dose-dependent manner. Western blotting results showed Sp1 overexpression increased Bak expression both in liver immortal non-tumour cells and HCC cells. Interference Sp1 expression could inhibit Bak expression alone. ZBP-89 siRNA suppressed Bak expression even in the presence of MMA treatment and S1 overexpression. Additionally, Bak and Sp1 level were associated with HCC patient survival.ConclusionsBak expression required ZBP-89 and Sp1 cooperative regulation simultaneously.
Highlights
Kruppel family member zinc binding protein 89 (ZBP-89), known as ZNF148, regulates Bak expression via binding to GC-rich promoter domain
Because Sp1 transcription factor (Sp1) itself did not bind to the promoter element, ZBP-89 interacted with Sp1 to suppress Vimentin expression in vitro [12]
This study focuses on the elucidation of transcription factor Sp1/Sp3 and ZBP-89 involved Bak expression
Summary
Kruppel family member zinc binding protein 89 (ZBP-89), known as ZNF148, regulates Bak expression via binding to GC-rich promoter domain. It is not clear if other GC-rich binding factors, such as Sp family members, can interact with ZBPp-89 on Bak expression. Because Sp1 itself did not bind to the promoter element, ZBP-89 interacted with Sp1 to suppress Vimentin expression in vitro [12]. In another case, ZBP-89 binded to the basal promoter of Pdcd, interacted with Sp family members to induce Pdcd protein expression [13]
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