ZHX2 is a repressor of α‐fetoprotein expression in human hepatoma cell lines

Shen, Huimin; Luan, Fang; Liu, H.; Gao, Liang; Liang, Xiaohong; Zhang, L.; Sun, Wenbo; Ma, Chaoqun

doi:10.1111/j.1582-4934.2008.00233.x

Cited by 50 publications

(59 citation statements)

References 32 publications

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“…For example cancer cells may carry out increased de novo fatty acid synthesis irrespective of extracellular lipid levels [Kuhajda, 2000;Menendez and Lupu, 2007]. In addition cancer cells including HepG2 cells express high levels of a-fetoprotein which is involved in lipid metabolism [Kumbla et al, 1991;Mizejewski, 2004;Shen et al, 2008]. Thus in the present study we first prepared steatotic cells using the L-02 cell line, which is derived from normal human hepatocytes.…”

Section: Discussionmentioning

confidence: 98%

ERp57 is up‐regulated in free fatty acids‐induced steatotic L‐02 cells and human nonalcoholic fatty livers

Wang

Chan

Pan

et al. 2010

J of Cellular Biochemistry

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Pathogenesis of nonalcoholic fatty liver disease (NAFLD) is not clear. In this study we aimed to identify proteins involved in NAFLD development in free fatty acids (FFA)-induced hepatosteatotic cells and in human liver biopsies. Steatosis was induced by incubating a normal human hepatocyte-derived cell line L-02 with FFA. Differentially expressed proteins in the steatotic cells were analyzed by two-dimensional gel electrophoresis-based proteomics. Involvement of one of the up-regulated proteins in steatosis was characterized using the RNA interference approach with the steatotic cells. Protein expression levels in liver biopsies of patients with NAFLD were assessed by immunohistochemistry. Proteomic analysis of L-02 steatotic cells revealed the up-regulation of ERp57, a condition not previously implicated in NAFLD. Knockdown of ERp57 expression with siRNA significantly reduced fat accumulation in the steatotic cells. ERp57 expression was detected in 16 out of 17 patient biopsies and correlated with inflammation grades or fibrosis stages, while in 5 normal biopsies ERp57 expression was not detectable in hepatocytes. In conclusion, ERp57 was up-regulated in FFA-induced steatotic hepatic cells and in NAFLD patient livers and demonstrated steatotic properties in cultured cells. Further investigations are warranted to verify the involvement of ERp57 in NAFLD development.

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Section: Discussionmentioning

confidence: 98%

ERp57 is up‐regulated in free fatty acids‐induced steatotic L‐02 cells and human nonalcoholic fatty livers

Wang

Chan

Pan

et al. 2010

J of Cellular Biochemistry

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“…They also found that AFP expression in BALB/cJ mouse liver was caused by the ZHX2 mutation. Shen et al 22 found ZHX2 interacted with hepatocyte NF-1 binding sites to repress AFP transcription in HCC cell lines. Furthermore, a clinical study demonstrated that ZHX2 expression is negatively related with AFP expression in HCC samples.…”

Section: Zhxs Signalingmentioning

confidence: 99%

Zinc fingers and homeoboxes family in human diseases

Liu

2015

Cancer Gene Ther

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The zinc-fingers and homeoboxes (ZHX) family is a group of nuclear homodimeric transcriptional repressors that interact with a subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. The members of ZHX family form homodimers or heterodimers with other members or a subunit of NF-YA to repress transcription. ZHX family members function in hematopoietic cell development and differentiation, and neural progenitor maintenance. Dysfunction of ZHX family members correlates with the development and progression of various diseases, including hepatocellular carcinoma (HCC), hematological diseases, neurological diseases and glomerular diseases. Furthermore, low expression of ZHX is associated with poor prognosis in malignancies. This review provides an update on the role of ZHX family in development and its function in cancer, with special emphasis on HCC and hematological malignant diseases.

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“…ZHX2 8 comprise 873 amino acid residues and shares two C2H2-typed zinc finger domains and five homeodomains with other members of the family, i.e., ZHX1 and ZHX3. In previous studies 9,10 , ZHX2 expressed ubiquitously in various tissues, and was identified as a transcriptional repressor for foetal-expressed genes, e.g., α-foetoprotein and glypican. The homeobox genes generally encode transcription factors that can either activate or repress target genes in a temporal and spatial manner 11 .…”

Section: Introductionmentioning

confidence: 94%

“…Loss of ZHX2 function in the liver causes persistent α-foetoprotein production in adult mice. Suppression of α-foetoprotein production in hepatocellular cancer cell line by ZHX2 is dependent on the HNF1 binding site 9 . Taken together, by an unknown mechanism, ZHX2 with or without other transcription factor(s) might be involved in the switching off of the γ-globin gene during adulthood.…”

Section: Introductionmentioning

confidence: 95%

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Panya¹,

Sawasdee²,

Srisawat

et al. 2010

ScienceAsia

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During the last few decades, foetal haemoglobin reactivation has been considered as a promising intervention to treat β-thalassaemia and sickle-cell anaemia. Variable foetal haemoglobin (Hb F, α2γ2) production among individuals is under control of distinct chromosome regions, namely, the quantitative trait loci (QTL). One of the QTL affecting Hb F levels on chromosome 8q has never been explored. The zinc fingers and homeodomains 2 (ZHX2) transcription factor located at 8q position is remarkably down-regulated in hereditary persistence of foetal haemoglobin, indicating an inverse correlation between the γ-globin and ZHX2 expression. Here we studied the effect of ZHX2 over the γ-globin expression in K562 erythroleukaemic cell line by transient transfection with a ZHX2 expression plasmid. At 24 h after transfection, the relative expression of endogenous γ-globin mRNA had been reduced to 0.401 ± 0.08 as assessed by real-time PCR. Our finding suggests that the repressive effect on γ-globin probably results from the presence of ZHX2 and supports its possible involvement in the regulation of γ-globin expression.

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ZHX2 is a repressor of α‐fetoprotein expression in human hepatoma cell lines

Cited by 50 publications

References 32 publications

ERp57 is up‐regulated in free fatty acids‐induced steatotic L‐02 cells and human nonalcoholic fatty livers

ERp57 is up‐regulated in free fatty acids‐induced steatotic L‐02 cells and human nonalcoholic fatty livers

Zinc fingers and homeoboxes family in human diseases

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