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CIDE-3 interacts with lipopolysaccharide-induced tumor necrosis factor, and overexpression increases apoptosis in hepatocellular carcinoma

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Abstract

Cell death–inducing DFF45-like effector-3 (CIDE-3) is a novel member of an apoptosis-inducing protein family, but its function is unknown. CIDE-3 shows a different distribution pattern in hepatocellular carcinoma (HCC) tissues and normal adjacent tissues. Therefore, this work tested the hypothesis that CIDE-3 induces apoptosis in HCC cells, inhibiting oncogenesis and tumor development. We used immunohistochemistry to evaluate the expression of CIDE-3 in 82 HCC samples and 51 adjacent liver tissues. Overexpression of CIDE-3 induced apoptosis, as detected by flow cytometry, in the HCC cell line SMMC-7721, which had undetectable levels of CIDE-3 in the absence of CIDE-3 overexpression. A yeast two-hybrid system was employed to screen for proteins that interact with CIDE-3. The expression of CIDE-3 was decreased in HCC tissue, compared to adjacent normal tissues, and CIDE-3 expression and HCC differentiation were positively correlated. CIDE-3 expression levels were lower in poorly differentiated HCC tissue than in well-differentiated HCC tissue. Overexpressed CIDE-3 inhibited proliferation and induced apoptosis in HCC cells. We found that lipopolysaccharide-induced tumor necrosis factor (LITAF) interacted with CIDE-3 in hepatic cells. This is the first demonstrated interaction between CIDE-3 and LITAF, and the first report that CIDE-3 induces apoptosis in hepatocellular carcinoma.

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Abbreviations

CIDE-3:

Cell death–inducing DFF45-like effector-3

LITAF:

Lipopolysaccharide-induced tumor necrosis factor

HCC:

Hepatocellular carcinoma

DFF:

DNA fragmentation factor

CAD:

Caspase-activated DNase

PBS:

Phosphate-buffered saline

DAB:

Diaminobenzidine

PVDF:

Polyvinylidene difluoride

TBS:

Tris-buffered saline

ORF:

Open reading frame

LPS:

Lipopolysaccharide

NO:

Nitric oxide

FISH:

Fluorescence in situ hybridization

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Authors and Affiliations

  1. State key laboratory of cancer biology, Department of pathology, Xijing Hospital, The Fourth Military Medical University, 710032, Xi’an, China

    Jie Min, Yu Gu, Liu Hong, Li Yao, Fanfan Li, Daqing Zhao & Qing Li

  2. Department of Biopharmaceutics, The Fourth Military Medical University, Xi’an, China

    Wei Zhang

  3. Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, 710032, Xi’an, China

    Jie Min, Yingming Feng & Helong Zhang

Authors
  1. Jie Min
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  2. Wei Zhang
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  3. Yu Gu
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  4. Liu Hong
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  5. Li Yao
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  10. Qing Li
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Correspondence to Qing Li.

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Jie Min, Wei Zhang and Yu Gu contributed equally to this work.

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Min, J., Zhang, W., Gu, Y. et al. CIDE-3 interacts with lipopolysaccharide-induced tumor necrosis factor, and overexpression increases apoptosis in hepatocellular carcinoma. Med Oncol 28 (Suppl 1), 219–227 (2011). https://doi.org/10.1007/s12032-010-9702-1

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  • DOI: https://doi.org/10.1007/s12032-010-9702-1

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