Effect and mechanism of acetyl-CoA carboxylase 1 in regulating the proliferation of hepatocellular carcinoma cells

JIAN Ani; BAI Xuexia; YANG Nanfei; SHEN Pingping

doi:10.11665/j.issn.1000-5048.2024032002

Journal of China Pharmaceutical University > 2024 > 55(6): 783-794. > DOI: 10.11665/j.issn.1000-5048.2024032002

JIAN Ani, BAI Xuexia, YANG Nanfei, et al. Effect and mechanism of acetyl-CoA carboxylase 1 in regulating the proliferation of hepatocellular carcinoma cells[J]. J China Pharm Univ, 2024, 55(6): 783 − 794. DOI: 10.11665/j.issn.1000-5048.2024032002

Citation:

PDF (2626 KB)

Effect and mechanism of acetyl-CoA carboxylase 1 in regulating the proliferation of hepatocellular carcinoma cells

School of Life Sciences, Nanjing University, Nanjing 210023, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 82304492，No.82300139)

More Information

Received Date: March 19, 2024

Graphical Abstract

Abstract

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 LD^high 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.

FullText(HTML)

References (24)

References

[1]	Vogel A, Meyer T, Sapisochin G, et al. Hepatocellular carcinoma[J]. Lancet, 2022, 400(10360): 1345-1362. doi: 10.1016/S0140-6736(22)01200-4
[2]	Nagaraju GP, Dariya B, Kasa P, et al. Epigenetics in hepatocellular carcinoma[J]. Semin Cancer Biol, 2022, 86(Pt 3): 622-632.
[3]	Duan JX, Zhu P, Zhang Y, et al. Single-cell RNA-seq revealed that altered tumor infiltrating lymphocytes in cirrhotic liver indicate development of hepatocellular carcinoma[J]. J Clin Transl Hepatol, 2023, 11(4): 850-862.
[4]	Bilotta MT, Antignani A, Fitzgerald DJ. Managing the TME to improve the efficacy of cancer therapy[J]. Front Immunol, 2022, 13: 954992. doi: 10.3389/fimmu.2022.954992
[5]	Tang BF, Zhu JY, Wang YJ, et al. Targeted xCT-mediated ferroptosis and protumoral polarization of macrophages is effective against HCC and enhances the efficacy of the anti-PD-1/L1 response[J]. Adv Sci, 2023, 10(2): e2203973. doi: 10.1002/advs.202203973
[6]	Xie M, Lin ZY, Ji XY, et al. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2[J]. J Hepatol, 2023, 79(1): 109-125. doi: 10.1016/j.jhep.2023.02.036
[7]	Timperi E, Gueguen P, Molgora M, et al. Lipid-associated macrophages are induced by cancer-associated fibroblasts and mediate immune suppression in breast cancer[J]. Cancer Res, 2022, 82(18): 3291-3306. doi: 10.1158/0008-5472.CAN-22-1427
[8]	Paul B, Lewinska M, Andersen JB. Lipid alterations in chronic liver disease and liver cancer[J]. JHEP Rep, 2022, 4(6): 100479. doi: 10.1016/j.jhepr.2022.100479
[9]	Jin HY, He Y, Zhao PF, et al. Targeting lipid metabolism to overcome EMT-associated drug resistance via integrin β3/FAK pathway and tumor-associated macrophage repolarization using legumain-activatable delivery[J]. Theranostics, 2019, 9(1): 265-278. doi: 10.7150/thno.27246
[10]	He YJ, Dong YX, Zhang XW, et al. Lipid droplet-related PLIN2 in CD68⁺ tumor-associated macrophage of oral squamous cell carcinoma: implications for cancer prognosis and immunotherapy[J]. Front Oncol, 2022, 12: 824235. doi: 10.3389/fonc.2022.824235
[11]	Bacci M, Lorito N, Smiriglia A, et al. Fat and furious: lipid metabolism in antitumoral therapy response and resistance[J]. Trends Cancer, 2021, 7(3): 198-213. doi: 10.1016/j.trecan.2020.10.004
[12]	Cheng LL, Deepak RNVK, Wang GQ, et al. Hepatic mitochondrial NAD + transporter SLC25A47 activates AMPKα mediating lipid metabolism and tumorigenesis[J]. Hepatology, 2023, 78(6): 1828-1842. doi: 10.1097/HEP.0000000000000314
[13]	Mossmann D, Müller C, Park S, et al. Arginine reprograms metabolism in liver cancer via RBM39[J]. Cell, 2023, 186 (23): 5068-5083. e23.
[14]	Filali-Mouncef Y, Hunter C, Roccio F, et al. The ménage à trois of autophagy, lipid droplets and liver disease[J]. Autophagy, 2022, 18(1): 50-72. doi: 10.1080/15548627.2021.1895658
[15]	Myers KV, Amend SR, Pienta KJ. Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment[J]. Mol Cancer, 2019, 18(1): 94. doi: 10.1186/s12943-019-1022-2
[16]	Ritterhoff J, Young S, Villet O, et al. Metabolic remodeling promotes cardiac hypertrophy by directing glucose to aspartate biosynthesis[J]. Circ Res, 2020, 126(2): 182-196. doi: 10.1161/CIRCRESAHA.119.315483
[17]	Yang YF, Luo DK, Shao Y, et al. circCAPRIN1 interacts with STAT2 to promote tumor progression and lipid synthesis via upregulating ACC1 expression in colorectal cancer[J]. Cancer Commun, 2023, 43(1): 100-122. doi: 10.1002/cac2.12380
[18]	Yu Y, Nie QZ, Wang ZY, et al. Targeting acetyl-CoA carboxylase 1 for cancer therapy[J]. Front Pharmacol, 2023, 14: 1129010. doi: 10.3389/fphar.2023.1129010
[19]	Gouda P, Kay R, Habib M, et al. Clinical features and complications of Loeys-Dietz syndrome: a systematic review[J]. Int J Cardiol, 2022, 362: 158-167. doi: 10.1016/j.ijcard.2022.05.065
[20]	Chen LY, Duan YQ, Wei HQ, et al. Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1/2 inhibitors[J]. Expert Opin Investig Drugs, 2019, 28(10): 917-930. doi: 10.1080/13543784.2019.1657825
[21]	Lally JSV, Ghoshal S, DePeralta DK, et al. Inhibition of acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma[J]. Cell Metab, 2019, 29 (1): 174-182. e5.
[22]	Ye BY, Yin L, Wang QW, et al. ACC1 is overexpressed in liver cancers and contributes to the proliferation of human hepatoma Hep G2 cells and the rat liver cell line BRL 3A[J]. Mol Med Rep, 2019, 19(5): 3431-3440.
[23]	Cao HY, Cai QX, Guo WR, et al. Malonylation of Acetyl-CoA carboxylase 1 promotes hepatic steatosis and is attenuated by ketogenic diet in NAFLD[J]. Cell Rep, 2023, 42(4): 112319. doi: 10.1016/j.celrep.2023.112319
[24]	Wu D, Yang Y, Hou YR, et al. Increased mitochondrial fission drives the reprogramming of fatty acid metabolism in hepatocellular carcinoma cells through suppression of Sirtuin 1[J]. Cancer Commun, 2022, 42(1): 37-55. doi: 10.1002/cac2.12247

[1]	WANG Shihao, LIU Lifeng, DING Yang, LI Suxin. Research progress of pH-responsive drug delivery systems in cancer immunotherapy[J]. Journal of China Pharmaceutical University, 2024, 55(4): 522-529. DOI: 10.11665/j.issn.1000-5048.2024011902
[2]	WU Yaqi, LI Meng, XING Haonan, CHEN Daquan, ZHENG Aiping. Research progress of nasal mucosal immunization vaccine against COVID-19[J]. Journal of China Pharmaceutical University, 2022, 53(6): 643-650. DOI: 10.11665/j.issn.1000-5048.20220602
[3]	BAO Xiaoqiang. Effects of co-culture supernatant of Lactobacillus casei and Bacillus subtiliis natto on intestinal microecology, mucosal barrier function and immune function in mice with antibiotic-associated diarrhea[J]. Journal of China Pharmaceutical University, 2020, 51(1): 92-98. DOI: 10.11665/j.issn.1000-5048.20200114
[4]	JIANG Liangliang, JIANG Tao, LUO Jianhua, YAO Wenbing, TIAN Hong. A novel human immune system mice model for assessing the immunogenicity of cancer vaccines[J]. Journal of China Pharmaceutical University, 2019, 50(6): 734-742. DOI: 10.11665/j.issn.1000-5048.20190615
[5]	HE Yu, TIAN Hong, DAI Xin, YAO Wenbing, GAO Xiangdong. Immunogenicity of HER2 vaccine containing p-nitrophenylalanine[J]. Journal of China Pharmaceutical University, 2018, 49(3): 369-375. DOI: 10.11665/j.issn.1000-5048.20180317
[6]	HAO Tianyun, GAO Yuan, WEI Yuanfeng, ZHANG Jianjun, QIAN Shuai. Strategies in transdermal and mucosal drug delivery systems:role of lyotropic liquid crystal[J]. Journal of China Pharmaceutical University, 2018, 49(2): 173-180. DOI: 10.11665/j.issn.1000-5048.20180206
[7]	NING Hongyu, JIANG Tao, ZHANG Rui, HE Yu, YAO Wenbing, TIAN Hong. Effects of immunogenic HER2 on the differentiation of T-cell in mouse[J]. Journal of China Pharmaceutical University, 2018, 49(1): 102-108. DOI: 10.11665/j.issn.1000-5048.20180115
[8]	LU Wei-dong, LIN Yi-ju, DAI Yun-bo, YANG Xuan-xiang, MA Bo. Preparation and immunogenicity of influenza vaccine lyophilized liposomes[J]. Journal of China Pharmaceutical University, 2009, 40(3): 218-221.
[10]	Study on the Immunogenity of Antigen and Antigenic Epitope Displayed by Phage Display of pIII and pVIII[J]. Journal of China Pharmaceutical University, 2004, (6): 100-105.

Cited By

Cited by

Periodical cited type(1)

敖日格乐. 蝎毒抗菌肽在病原微生物感染中的作用. 中国病原生物学杂志. 2024(12): 1521-1524 .

Other cited types(0)

Get Citation

PDF

XML

Article views (72) PDF downloads (12) Cited by(1)

Turn off MathJax

Article Contents

Abstract

References

Effect and mechanism of acetyl-CoA carboxylase 1 in regulating the proliferation of hepatocellular carcinoma cells