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Targeting ODC1 inhibits tumor growth through reduction of lipid metabolism in human hepatocellular carcinoma

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Author(s)
Yunseon ChoiSang Taek OhMin-Ah WonKyung Mi ChoiMin Ji KoDaekwan SeoTae-Won JeonIn Hye BaikSang-Kyu YeKeon Uk ParkIn-Chul ParkByeong-Churl JangJun-Young SeoYun-Han Lee
Keimyung Author(s)
Jang, Byeong ChurlPark, Keon UkLee, Yun Han
Department
Dept. of Molecular Medicine (분자의학)
Dept. of Internal Medicine (내과학)
Journal Title
Biochemical and Biophysical Research Communications
Issued Date
2016
Volume
478
Issue
4
Keyword
HCCODC1PolyamineKLF2PPARγLipogenesis
Abstract
Ornithine decarboxylase 1 (ODC1), a metabolic enzyme critically involved in the polyamine biosynthesis, is commonly upregulated in hepatocellular carcinoma (HCC). Despite its altered expression in human HCC tissues, the molecular mechanism by which ODC1 alters the course of HCC progression and functions in HCC cell survival is unknown. Here we identified that silencing of ODC1 expression with small interfering (si) RNA causes inhibition of HCC cell growth through blockade of cell cycle progression and induction of apoptosis. Next, to obtain insights into the molecular changes in response to ODC1 knockdown, global changes in gene expression were examined using RNA sequencing. It revealed that 119 genes show same directional regulation (76 up- and 43 down-regulated) in both Huh1 and Huh7 cells and were considered as a common ODC1 knockdown signature. Particularly, we found through a network analysis that KLF2, which is known to inhibit PPARγ expression and adipogenesis, was commonly up-regulated. Subsequent Western blotting affirmed that the downregulation of ODC1 was accompanied by a decrease in the levels of PPARγ as well as of PARP-1, cyclin E1 and pro-caspase 9 delaying cell cycle progression and accelerating apoptotic signaling. Following the down-regulation of PPARγ expression, ODC1 silencing resulted in a strong inhibition in the expression of important regulators of glucose transport and lipid biogenesis, and caused a marked decrease in lipid droplet accumulation. In addition, ODC1 silencing significantly inhibited the growth of human HCC xenografts in nude mice. These findings indicate that the function of ODC1 is correlated with HCC lipogenesis and suggest that targeting ODC1 could be an attractive option for molecular therapy of HCC.
Keimyung Author(s)(Kor)
장병철
이윤한
박건욱
Publisher
School of Medicine
Citation
Yunseon Choi et al. (2016). Targeting ODC1 inhibits tumor growth through reduction of lipid metabolism in human hepatocellular carcinoma. Biochemical and Biophysical Research Communications, 478(4), 1674–1681. doi: 10.1016/j.bbrc.2016.09.002
Type
Article
ISSN
0006-291X
Source
https://linkinghub.elsevier.com/retrieve/pii/S0006291X16314449
DOI
10.1016/j.bbrc.2016.09.002
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32730
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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