ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway

doi:10.1002/mc.23777

科研成果详情

题名	ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway
作者	Cai, Qihong1; Zhu, Honghua1; Dai, Yile1; Zhou, Qingqing2; Zhang, Qiyu 1; Zhu, Qiandong1
发表日期	2024-06-18
发表期刊	Molecular Carcinogenesis 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	ATP citrate lyase hepatocellular carcinoma proteasome pathway REG gamma
其他关键词	CELL-CYCLE ; CANCER ; EXPRESSION ; PROLIFERATION ; INHIBITION ; DIAGNOSIS ; TARGET ; GROWTH
摘要	The search for novel tumor biomarkers and targets is of significant importance for the early clinical diagnosis and treatment of Hepatocellular Carcinoma (HCC). The mechanisms by which ATP citrate lyase (ACLY) promotes HCC progression remain unclear, and the connection between ACLY and REG gamma has not been reported in the literature. In vitro, we will perform overexpression/knockdown of ACLY or overexpression/knockdown of REG gamma to investigate the impact of ACLY on HCC cells and its underlying mechanisms. In vivo, we will establish mouse tumor models with overexpression/knockdown of ACLY or overexpression/knockdown of REG gamma to study the effect of ACLY on mouse tumors and its mechanisms. Firstly, ACLY overexpression upregulated REG gamma expression and activated the REG gamma-proteasome pathway, leading to changes in the expression of downstream signaling pathway proteins. This promoted HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Secondly, ACLY overexpression increased acetyl-CoA production, upregulated the acetylation level of the REG gamma promoter region histone H3K27ac, and subsequently induced REG gamma expression. Lastly, enhanced acetylation of the REG gamma promoter region histone H3K27ac resulted in upregulated REG gamma expression, activation of the REG gamma-proteasome pathway, changes in downstream signaling pathway protein expression, and promotion of HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Conversely, REG gamma knockdown reversed these effects. ACLY and REG gamma may serve as potential biomarkers and clinical therapeutic targets for HCC.
资助项目	Wenzhou Science and Technology Project; Province Key Surgery Projects [Zhejiang High-Tech 2008-255, Zhejiang High-Tech 2012-80, 2016-169]; [Y20210172]
出版者	WILEY
ISSN	0899-1987
EISSN	1098-2744
卷号	63 期号:10 页码:1874-1891
DOI	10.1002/mc.23777
页数	18
WOS类目	Biochemistry & Molecular Biology ; Oncology
WOS研究方向	Biochemistry & Molecular Biology ; Oncology
WOS记录号	WOS:001248787300001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	38888205
SCOPUSEID	2-s2.0-85196199495
通讯作者地址	[Zhang, Qiyu;Zhu, Qiandong]Wenzhou Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Nanbaixiang St, Wenzhou 325000, Zhejiang, Peoples R China.
Scopus学科分类	Molecular Biology;Cancer Research
SCOPUS_ID	SCOPUS_ID:85196199495
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/215311
专题	附属第一医院附属第一医院_肝胆外科附属第一医院_护理部
通讯作者	Zhang, Qiyu; Zhu, Qiandong
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Nanbaixiang St, Wenzhou 325000, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Dept Nursing, Wenzhou, Peoples R China
第一作者单位	附属第一医院; 肝胆外科
通讯作者单位	附属第一医院; 肝胆外科
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Cai, Qihong,Zhu, Honghua,Dai, Yile,et al. ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway[J]. Molecular Carcinogenesis,2024,63(10):1874-1891.
APA	Cai, Qihong, Zhu, Honghua, Dai, Yile, Zhou, Qingqing, Zhang, Qiyu, & Zhu, Qiandong. (2024). ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway. Molecular Carcinogenesis, 63(10), 1874-1891.
MLA	Cai, Qihong,et al."ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway".Molecular Carcinogenesis 63.10(2024):1874-1891.