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ATG5 interacts with the p53 signaling pathway to promote the development of hepatocellular carcinoma
Received:November 08, 2022  Revised:January 02, 2023  Click here to download the full text
Citation of this paper:GUO Hong-ying,ZHANG Wan-qin,LIU Zhi-yong,YU Xiang-nan,ZHU Ji-min,LIU Tao-tao,DONG Ling,SHEN Xi-zhong.ATG5 interacts with the p53 signaling pathway to promote the development of hepatocellular carcinoma[J].Chinese Journal of Clinical Medicine,2023,30(1):72-79
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Author NameAffiliationE-mail
GUO Hong-ying Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Department of Severe Hepatitis Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China 
 
ZHANG Wan-qin Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China  
LIU Zhi-yong Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China  
YU Xiang-nan Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China  
ZHU Ji-min Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China  
LIU Tao-tao Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China  
DONG Ling Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China  
SHEN Xi-zhong Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China shen.xizhong@zs-hospital.sh.cn 
Abstract:Objective To explore the role and the signaling pathways of autophagy-related gene 5 (ATG5) in hepatocellular carcinoma (HCC). Methods The Cancer Genome Atlas (TCGA) database was used to investigate the expression of ATG5 in HCC tissues and differential analysis in its subgroups. Western blotting was performed to clarify its expression in HCC cell lines. Cell Counting Kit-8, wound healing assay, and Transwell assay were employed to unveil the function of ATG5 in HCCLM3 and MHCC97-H cells. RNA Sequencing and differentially expressed genes analysis were performed to discover the relevant signaling pathways. Results TCGA database showed that the mRNA expression of ATG5 was significantly higher in HCC tissues compared with that in normal liver tissues (P<0.000 1), and higher expression in patients at stage 3 than those at stage 1 (P=0.013). Furthermore, its expression was higher in patients with p53 mutation (P<0.000 1). Western blotting results showed that the levels of ATG5 were significantly higher in all tested HCC cell lines than L02. Knockdown of ATG5 was found to inhibits HCC cell proliferation, migration, and invasion, and it was also revealed to affect the expression of p53-related signaling pathway, cell cycle and autophagy-related pathway. Conclusions ATG5 downregulation inhibited the function of HCC cells and promoted HCC progression by affecting the p53 signaling pathway.
keywords:hepatocellular carcinoma  autophagy-related gene5  p53 signaling pathway
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