Yan Zhengyuan, Liu Kanghui, Xu Peng, Chen Zhengwei, Zhang Pengpeng, Pei Shengbin, Cheng Quan, Huang Shansong, Li Bowen, Lv Jialun, Xu Zekuan, Xu Hao, Yang Li, Zhang Diancai
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Surgery, Nanjing Lishui People's Hospital, Nanjing, China.
Cell Cycle. 2023 Oct;22(20):2288-2301. doi: 10.1080/15384101.2023.2286805. Epub 2023 Dec 15.
Mounting evidence indicates the potential involvement of ATP-citrate lyase (ACLY) in the modulation of various cancer types. Nevertheless, the precise biological significance of ACLY in gastric cancer (GC) remains elusive. This study sought to elucidate the biological function of ACLY and uncover its influence on peritoneal metastasis in GC. The expression of ACLY was assessed using both real-time quantitative PCR and western blot techniques. To investigate the impact of ACLY on the proliferation of gastric cancer (GC) cells, colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed. The migratory and invasive abilities of GC were evaluated using wound healing and transwell assays. Additionally, a bioinformatics analysis was employed to predict the correlation between ACLY and HIF-1A. This interaction was subsequently confirmed through a chromatin immunoprecipitation (ChIP) assay. ACLY exhibited upregulation in gastric cancer (GC) as well as in peritoneal metastasis. Its overexpression was found to facilitate the proliferation and metastasis of GC cells in both in vitro and in vivo experiments. Moreover, ACLY was observed to play a role in promoting angiogenesis and epithelial-mesenchymal transition (EMT). Notably, under hypoxic conditions, HIF-1A levels were elevated, thereby acting as a transcription factor to upregulate ACLY expression. Under the regulatory influence of HIF-1A, ACLY exerts a significant impact on the progression of gastric cancer, thereby facilitating peritoneal metastasis.
越来越多的证据表明，ATP柠檬酸裂解酶（ACLY）可能参与多种癌症类型的调控。然而，ACLY在胃癌（GC）中的精确生物学意义仍不清楚。本研究旨在阐明ACLY的生物学功能，并揭示其对胃癌腹膜转移的影响。采用实时定量PCR和蛋白质印迹技术评估ACLY的表达。为了研究ACLY对胃癌（GC）细胞增殖的影响，进行了集落形成和5-乙炔基-2'-脱氧尿苷（EdU）检测。采用伤口愈合和Transwell检测评估GC的迁移和侵袭能力。此外，利用生物信息学分析预测ACLY与HIF-1A之间的相关性。随后通过染色质免疫沉淀（ChIP）检测证实了这种相互作用。ACLY在胃癌（GC）以及腹膜转移中均表现出上调。在体外和体内实验中均发现其过表达促进GC细胞的增殖和转移。此外，观察到ACLY在促进血管生成和上皮-间质转化（EMT）中发挥作用。值得注意的是，在缺氧条件下，HIF-1A水平升高，从而作为转录因子上调ACLY表达。在HIF-1A的调控影响下，ACLY对胃癌的进展产生显著影响，从而促进腹膜转移。
