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. 2018 Mar 13;5(3):e1441627.
doi: 10.1080/23723556.2018.1441627. eCollection 2018.

Cisd2 haploinsufficiency: A driving force for hepatocellular carcinoma

Zhao-Qing Shen  1 , Yi-Long Huang  1 , Ting-Fen Tsai  1   2   3   4
Affiliations

Cisd2 haploinsufficiency: A driving force for hepatocellular carcinoma

Zhao-Qing Shen et al. Mol Cell Oncol. .

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is the major risk factor leading to hepatocellular carcinoma (HCC). Cisd2 haploinsufficiency in mice causes NAFLD by disrupting Ca2+ homeostasis, indicating that CISD2 is a molecular target for the treatment of NAFLD and the prevention of HCC.

Keywords: CISD2; ER stress; Serca2b; calcium homeostasis; haploinsufficiency; hepatocellular carcinoma; nonalcoholic fatty liver disease; tumor suppressor gene.

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Figures

Figure 1.
Figure 1.
CISD2 as a potential therapeutic drug target for the treatment of NAFLD and NASH, and the prevention of HCC. A, In mice, CDGSH iron sulfur domain 2 (Cisd2) haploinsufficiency impairs sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 isoform b (Serca2b) activity and disrupts Ca2+ homeostasis leading to non-alcoholic fatty liver disease (NAFLD). While obesity impairs Serca2b activity via a decrease in Serca2b protein level. B, In human, CISD2 and SERCA2b are both possible drug targets for the treatment of NAFLD and the prevention of hepatocellular carcinoma (HCC). In addition to directly target SERCA2b, CISD2 activators may have the potential to treat NAFLD indirectly by enhancing SERCA2b activity through an increase in CISD2 protein level. ER, endoplasmic reticulum; HBV, hepatitis B virus; HFD, high fat diet; NASH, nonalcoholic steatohepatitis.
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