Effect and mechanism of acetyl-CoA carboxylase 1 in regulating the proliferation of hepatocellular carcinoma cells
10.11665/j.issn.1000-5048.2024032002
- VernacularTitle:乙酰辅酶 A 羧化酶调控肝癌细胞增殖的效应与机制
- Author:
Ani JIAN Ani
1
;
Xuexia BAI
;
Nanfei YANG
;
Pingping SHEN
Author Information
1. 南京大学生命科学学院, 南京210023
- Publication Type:Journal Article
- Keywords:
hepatocellular carcinoma / tumor-associated macrophages / metabolic reprogramming / lipid droplets / acetyl coenzyme A carboxylase alpha（ACC1）
- From:
Journal of China Pharmaceutical University
2024;55(6):783-794
- CountryChina
- Language:Chinese
-
Abstract:
In order to investigate how macrophages promote lipid droplet hoarding in hepatocellular carcinoma cells and to delve into the roles of key metabolic enzymes of lipid droplets in the malignant biology of hepatocellular carcinoma cells, the present study was conducted to induce the generation of Hepa1-6 lipid droplets (LDs) using supernatants from tumor-associated macrophages (TAMs), and found that interleukin-10 (IL-10) in TAMs was found to promote the accumulation of lipid droplets. Acetyl-CoA carboxylase alpha (ACC1) is one of the key enzymes for fatty acid synthesis and influences the development of hepatocellular carcinoma. In this study, ACC1 was found to be highly expressed in LDhigh Hepa1-6, and subsequent blockade of ACC1 activity by means of a small molecule inhibitor of ACC1, siRNA interference, and CRISPR-cas9 knockdown was found to reduce the accumulation of Hepa1-6 lipid droplets, as well as to reduce the malignant biological behavior of Hepa1-6 proliferation, and to promote the occurrence of apoptotic events. In summary, IL-10 released by TAMs promoted lipid droplet formation in hepatocellular carcinoma cells, leading to malignant proliferation and apoptosis of hepatocellular carcinoma cells. ACC1 plays a key role in the promotion of lipid droplet accumulation in hepatocellular carcinoma cells by TAMs and may be regulated by IL-10 released by TAMs, and these findings may provide a new target for hepatocellular carcinoma treatment.
