DAGLβ is the principal synthesizing enzyme of 2-AG and promotes aggressive phenotype of intrahepatic cholangiocarcinoma via AP-1/DAGLβ/miR4516 feedforward circuitry-Reference-Cited by-同舟云学术

DAGLβ is the principal synthesizing enzyme of 2-AG and promotes aggressive phenotype of intrahepatic cholangiocarcinoma via AP-1/DAGLβ/miR4516 feedforward circuitry

Published:2023-09-01 Issue:3 Volume:325 Page:G213-G229
ISSN:0193-1857
Container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology
language:en
Short-container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology

Author:

Ma Mingjian¹²,Zeng Guangyan¹²³,Tan Bingyan⁴,Zhao Guangyin⁵,Su Qiao⁵,Zhang Wenhui⁶,Song Yan⁶,Liang Jiahua¹²,Xu Borui¹²,Wang Zicheng¹²,Chen Jiancong¹²^ORCID,Hou Mengjun⁴,Yang Chuntao⁷,Yun Jingping⁸⁹,Huang Yuhua⁸⁹,Lin Yansong⁸⁹,Chen Demeng¹⁰,Han Yuyan¹¹,DeMorrow Sharon¹²¹³¹⁴,Liang Lijian¹²,Lai Jiaming¹²,Huang Li¹²^ORCID

Affiliation:

1. Department of Pancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China

2. Center of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China

3. Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China

4. Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China

5. Laboratory Animal Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China

6. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China

7. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Key Laboratory of Protein Modification and Degradation, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, People’s Republic of China

8. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China

9. Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China

10. Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China

11. School of Biological Sciences, University of Northern Colorado, Greeley, Colorado, United States

12. Research Division, Central Texas Veterans Health Care System, Temple, Texas, United States

13. Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, United States

14. Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, Texas, United States

Abstract

Dysregulated endocannabinoid system (ECS) had been confirmed in various liver diseases. However, regulation and function of 2-arachidonoyl glycerol (2-AG) and diacylglycerol lipase β (DAGLβ) in intrahepatic cholangiocarcinoma (ICC) remain to be elucidated. Here, we demonstrated that 2-AG was enriched in ICC, and DAGLβ was the principal synthesizing enzyme of 2-AG in ICC. DAGLβ promotes tumorigenesis and metastasis in ICC via a novel activator protein-1 (AP-1)/DAGLβ/miR4516 feedforward circuitry.

Funder

Natural Science Foundation of Guangdong Province

MOST | NSFC | National Natural Science Foundation of China-Shenzhen Robotics Research Center Project

MOST | National Natural Science Foundation of China

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpgi.00243.2022

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