ACLY-β-catenin axis modulates hepatoblastoma cell proliferation

Yanyan Lin; Houshun Fang; Chunshuang Ma; Jiquan Zhou; Ming Ding; Huiying Sun; Yan Xu; Yuhua Shan; Hongxiang Gao; Liyuan Yang; Song Gu; Hui Li

doi:10.1016/j.bbrc.2023.04.074

ACLY-β-catenin axis modulates hepatoblastoma cell proliferation

Biochem Biophys Res Commun. 2023 Jun 30:663:104-112. doi: 10.1016/j.bbrc.2023.04.074. Epub 2023 Apr 24.

Authors

Yanyan Lin¹, Houshun Fang², Chunshuang Ma³, Jiquan Zhou⁴, Ming Ding⁵, Huiying Sun⁶, Yan Xu⁷, Yuhua Shan⁸, Hongxiang Gao⁹, Liyuan Yang¹⁰, Song Gu¹¹, Hui Li¹²

Affiliations

¹ Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: lyy18951897@126.com.
² Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: fanghoushun19@126.com.
³ Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: m13142084483@163.com.
⁴ Department of General Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: zhone2018@163.com.
⁵ Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: kimi-ting@outlook.com.
⁶ Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: SunHY0801@126.com.
⁷ Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: xuyan.91@outlook.com.
⁸ Department of General Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: danyuhua@scmc.com.cn.
⁹ Department of General Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: gaohongxiang@scmc.com.cn.
¹⁰ Department of General Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: liyuan2079@163.comss.
¹¹ Department of General Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: gusong@shsmu.edu.cn.
¹² Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China; Fujian Children's Hospital, Fujian Branch of Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Fujian, China. Electronic address: lihui@scmc.com.cn.

PMID: 37121120
DOI: 10.1016/j.bbrc.2023.04.074

Abstract

HB (hepatoblastoma) is most common in children with liver cancer and few options for treating HB. Thus, it is of great significance to investigate the regulatory mechanism of HB and/or identify new therapeutic targets for clinical treatment of HB. Here, we showed that ACLY (ATP citrate lyase), an important lipometabolic enzyme for de novo biosynthesis of fatty acids and steroids, has a higher expression in HB tissues than noncancerous tissues, and is required for HB cell proliferation. Moreover, knocking down ACLY in HB cells caused severe S-phase arrest and apoptosis. Mechanistically, ACLY knockdown significantly silenced the Wnt signaling pathway and reduced β-catenin expression in HB cells. Conversely, the apoptotic alleviation of HB cells by overexpressing ACLY was blocked by silencing β-catenin, suggesting the modulation of HB cells by ACLY-β-catenin axis. Our results uncovered the role of ACLY in HB cells and presented a theoretical approach for HB targeted therapy in the future.

Keywords: ATP citrate Lyase; Hepatoblastoma; Lipometabolism; Targeted therapy; β-catenin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Citrate (pro-S)-Lyase / metabolism
Cell Line, Tumor
Cell Proliferation
Child
Hepatoblastoma* / genetics
Humans
Liver Neoplasms* / genetics
Liver Neoplasms* / metabolism
beta Catenin / genetics

Substances

beta Catenin
ATP Citrate (pro-S)-Lyase