Nie AY, Xiao ZH, Deng JL, Li N, Hao LY, Li SH, Hu XY. Bidirectional regulation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene pathway and its impact on hepatocellular carcinoma. World J Gastrointest Oncol 2025; 17(2): 98556 [DOI: 10.4251/wjgo.v17.i2.98556]
Corresponding Author of This Article
Xiao-Yu Hu, MD, Professor, Department of Infection, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shierqiao Road, Jinniu District, Chengdu 610072, Sichuan Province, China. xiaoyuhu_dr@sina.com
Research Domain of This Article
Cell Biology
Article-Type of This Article
Systematic Reviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Feb 15, 2025; 17(2): 98556 Published online Feb 15, 2025. doi: 10.4251/wjgo.v17.i2.98556
Bidirectional regulation of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene pathway and its impact on hepatocellular carcinoma
Ai-Yu Nie, Zhong-Hui Xiao, Jia-Li Deng, Na Li, Li-Yuan Hao, Sheng-Hao Li, Xiao-Yu Hu
Ai-Yu Nie, Zhong-Hui Xiao, Jia-Li Deng, Na Li, Li-Yuan Hao, Sheng-Hao Li, College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
Xiao-Yu Hu, Department of Infection, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
Author contributions: Nie AY, Li N, Hao LY and Li SH contributed to idea and design; Xiao ZH and Deng JL contributed to literature search; Nie AY contributed to writing of manuscript; Hu XY contributed to approval of final manuscript.
Supported by the National Natural Science Foundation of China, No. 81973840; and the Sichuan Provincial Administration of Traditional Chinese Medicine Major Science and Technology projects, No. 2021XYCZ004.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Yu Hu, MD, Professor, Department of Infection, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shierqiao Road, Jinniu District, Chengdu 610072, Sichuan Province, China. xiaoyuhu_dr@sina.com
Received: June 29, 2024 Revised: October 30, 2024 Accepted: November 18, 2024 Published online: February 15, 2025 Processing time: 203 Days and 4.4 Hours
Abstract
BACKGROUND
Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related deaths in China, and the treatment options are limited. The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) activates the stimulator of interferon gene (STING) signaling pathway as a crucial immune response pathway in the cytoplasm, which detects cytoplasmic DNA to regulate innate and adaptive immune responses. As a potential therapeutic target, cGAS-STING pathway markedly inhibits tumor cell proliferation and metastasis, with its activation being particularly relevant in HCC. However, prolonged pathway activation may lead to an immunosuppressive tumor microenvironment, which fostering the invasion or metastasis of liver tumor cells.
AIM
To investigate the dual-regulation mechanism of cGAS-STING in HCC.
METHODS
This review was conducted according to the PRISMA guidelines. The study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science databases. Through rigorous screening and meticulous analysis of the retrieved literature, the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC tumors.
RESULTS
All authors collaboratively selected studies for inclusion, extracted data, and the initial search of online databases yielded 1445 studies. After removing duplicates, the remaining 964 records were screened. Ultimately, 55 articles met the inclusion criteria and were included in this review.
CONCLUSION
Acute inflammation can have a few inhibitory effects on cancer, while chronic inflammation generally promotes its progression. Extended cGAS-STING pathway activation will result in a suppressive tumor microenvironment.
Core Tip: As a crucial signaling pathway for both innate and adaptive immune responses, studies have demonstrated that cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway can be triggered by tumor DNA and genomic instability, thereby promoting or inhibiting tumor development and metastasis. A considerable amount of evidence indicates that the cGAS-STING pathway, as a potential therapeutic target, markedly inhibits tumor cell proliferation and metastasis, with its activation being particularly relevant in hepatocellular carcinoma. But at the same time, prolonged pathway activation may lead to an immunosuppressive tumor microenvironment, fostering liver damage, fibrosis, carcinogenesis, and the invasion or metastasis of liver tumor cells.
