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

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, Changzhou, 213000, China
2 Department of General Surgery, Changzhou No. 3 People’s Hospital, Changzhou, 213000, China
3 Department of Gastroenterology, Changzhou No. 1 People’s Hospital, Changzhou, 213000, China
4 Department of Liver Disease, Changzhou No. 3 People’s Hospital, Changzhou, 213000, China

* Address correspondence to: Jiakai Jiang, ; Suobao Xu,
# These authors have contributed equally to this work

BIOCELL 2022, 46(6), 1483-1491. https://doi.org/10.32604/biocell.2022.017745

Abstract

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.

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Cite This Article

XU, Y., WU, B., YANG, J., ZHANG, S., LIU, L. et al. (2022). Murine double minute gene 2 (MDM2) promoted hepatocellular carcinoma (HCC) cell growth by targeting fructose-1,6-bisphosphatase (FBP1) for degradation. BIOCELL, 46(6), 1483–1491.



This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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