ACLY promotes gastric tumorigenesis and accelerates peritoneal metastasis of gastric cancer regulated by HIF-1A

ABSTRACT

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.

KEYWORDS:

• ACLY
• gastric cancer
• tumorigenesis
• peritoneal metastasis
• HIF-1A

Acknowledgements

This study was supported by Jiangsu Province Capability Improvement Project through Science, Technology and Education (Jiangsu Provincial Medical Key Discipline,ZDXK202222) and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX21_0622).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Diancai Zhang conceptualized and supervised the research. Zhengyuan Yan, Kanghui Liu, Peng Xu and Zhengwei Chen designed and performed most experiments. Pengpeng Zhang, Shengbin Pei, Jialun Lv and Quan Cheng performed animal experiments. Shansong Huang, Xinyi Zhou and Bowen Li were engaged in biostatistics and bioinformatics analysis. Zekuan Xu is responsible for the collection of tissues and follow-up of patients

Data availability statement

The datasets generated during and analyzed during the current study are not publicly available due other members of our group need to use RNA-seq data but are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2023.2286805.

Additional information

Funding

The work was supported by the Jiangsu Province Capability Improvement Project through Science, Technology and Education [ZDXK202222]; Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX21_0622].