Murine double minute gene 2 (MDM2) promoted hepatocellular carcinoma (HCC) cell growth by targeting fructose-1,6-bisphosphatase (FBP1) for degradation

Biocell

article

YAO XU¹  BIN WU²  JING YANG³  SHENG ZHANG²  LONGGEN LIU⁴  SUOBAO XU²  JIAKAI JIANG² 

[1] Department of Intensive Care Unit, Changzhou No. 3 People’s Hospital;Department of General Surgery, Changzhou No. 3 People’s Hospital;Department of Gastroenterology, Changzhou No. 1 People’s Hospital;Department of Liver Disease, Changzhou No. 3 People’s Hospital

关键词: Human hepatocellular carcinoma;    MDM2;    FBP1;    FBP1 ubiquitination;   

DOI  :  10.32604/biocell.2022.017745

学科分类：仪器

来源: Biocell

【 摘 要 】

To study the roles and association of murine double minute gene 2 (MDM2) and fructose-1,6-biphosphatase (FBP1) in human hepatocellular carcinoma (HCC), growth response of human HCC cells was assessed using proliferation and apoptosis assay. Pro-survival AKT signaling associated proteins (p-AKT, survivin and cleaved caspase 3) were assessed using western blotting. The correlation between MDM2 and FBP1 was assessed using co-immunoprecipitation combined with ubiquitination assay. Our data suggested that low expression of FBP1 was correlated with high levels of MDM2 in HCC cell lines (Huh7 and Hep3B). Overexpression of FBP1 resulted in anti-proliferation, pro-apoptosis, the up-regulation of cleaved caspase 3 while the downregulation of survivin and phosphor (p)-AKT, however, knockdown of FBP1 led to the opposite. Furthermore, overexpression of MDM2 potently reversed FBP1-induced proliferation inhibition and apoptosis, while Nutlin-3 (an MDM2 inhibitor) reversed the change trends induced by FBP1 knockdown in the aforementioned events. Lastly, but not least importantly, our data elucidated that MDM2 binds directly to FBP1 and promotes FBP1 ubiquitination. In conclusion, our data firstly suggested the involvement of FBP1 and its association with MDM2 in HCC cell growth. MDM2-FBP1-regulated HCC cell growth and the activation of AKT were mediated, at least in part, through FBP1 degradation.

【 授权许可】

CC BY